Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer

Subhadip Kundu; M.D. Ray; Ashok Sharma

doi:10.1016/j.jgg.2021.02.004

Volume 48 Issue 3

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2021 > 48(3): 184-197

PDF( 1981 KB)

Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer

doi: 10.1016/j.jgg.2021.02.004

a
Laboratory of Chromatin and Cancer Epigenetics, Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
b
Department of Surgical Oncology, IRCH, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India

More Information

Corresponding author: E-mail address: ashoksharma1202@gmail.com (Ashok Sharma)
Received Date: 2020-09-06
Accepted Date: 2021-02-20
Rev Recd Date: 2021-02-07

Available Online: 2021-03-06

Publish Date: 2021-03-20

Abstract

Abstract

In eukaryotic genome biology, the genomic organization inside the three-dimensional (3D) nucleus is highly complex, and whether this organization governs gene expression is poorly understood. Nuclear lamina (NL) is a filamentous meshwork of proteins present at the lining of inner nuclear membrane that serves as an anchoring platform for genome organization. Large chromatin domains termed as lamina-associated domains (LADs), play a major role in silencing genes at the nuclear periphery. The interaction of the NL and genome is dynamic and stochastic. Furthermore, many genes change their positions during developmental processes or under disease conditions such as cancer, to activate certain sorts of genes and/or silence others. Pericentromeric heterochromatin (PCH) is mostly in the silenced region within the genome, which localizes at the nuclear periphery. Studies show that several genes located at the PCH are aberrantly expressed in cancer. The interesting question is that despite being localized in the pericentromeric region, how these genes still manage to overcome pericentromeric repression. Although epigenetic mechanisms control the expression of the pericentromeric region, recent studies about genome organization and genome-nuclear lamina interaction have shed light on a new aspect of pericentromeric gene regulation through a complex and coordinated interplay between epigenomic remodeling and genomic organization in cancer.
- LADs,
- Pericentromere,
- Heterochromatin,
- Gene regulation,
- Epigenetics,
- Cancer,
- Genome organization

FullText(HTML)

References(181)

References

[1]	Alcobia, I., Dilao, R., Parreira, L., 2000. Spatial associations of centromeres in the nuclei of hematopoietic cells: Evidence for cell-type-specific organizational patterns. Blood 95, 1608-1615.
[2]	Allshire, R.C., Madhani, H.D., 2018. Ten principles of heterochromatin formation and function. Nat. Rev. Mol. Cell Biol. 19, 229-244.
[3]	Alonso, A., Hasson, D., Cheung, F., Warburton, P.E., 2010. A paucity of heterochromatin at functional human neocentromeres. Epigenetics Chromatin 3, 6.
[4]	Ando-Kuri, M., Rivera, I.S.M., Rowley, M.J., Corces, V.G., 2018. Analysis of chromatin interactions mediated by specific architectural proteins in drosophila cells. Methods Mol. Biol. 1766, 239-256.
[5]	Bailey, J.A., Gu, Z., Clark, R.A., Reinert, K., Samonte, R. V., Schwartz, S., Adams, M.D., Myers, E.W., Li, P.W., Eichler, E.E., 2002. Recent segmental duplications in the human genome. Science 297, 1003-1007.
[6]	Bailey, J.A., Yavor, A.M., Massa, H.F., Trask, B.J., Eichler, E.E., 2001. Segmental duplications: Organization and impact within the current human genome project assembly. Genome Res. 11, 1005-1017.
[7]	Barger, C.J., Zhang, W., Sharma, A., Chee, L., James, S.R., Kufel, C.N., Miller, A., Meza, J., Drapkin, R., Odunsi, K. et al., 2018. Expression of the POTE gene family in human ovarian cancer. Sci. Rep. 8, 17136.
[8]	Bartholdi, M.F., 1991. Nuclear distribution of centromeres during the cell cycle of human diploid fibroblasts. J. Cell Sci. 99, 255-263.
[9]	Barutcu, A.R., Fritz, A.J., Zaidi, S.K., van Wijnen, A.J., Lian, J.B., Stein, J.L., Nickerson, J.A., Imbalzano, A.N., Stein, G.S., 2016. C-ing the cenome: A compendium of chromosome conformation capture methods to study higher-order chromatin organization. J. Cell. Physiol. 231, 31-35.
[10]	Barutcu, A.R., Lajoie, B.R., McCord, R.P., Tye, C.E., Hong, D., Messier, T.L., Browne, G., van Wijnen, A.J., Lian, J.B., Stein, J.L. et al., 2015. Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells. Genome Biol. 16, 214.
[11]	Bastian, B.C., LeBoit, P.E., Hamm, H., Brocker, E.B., Pinkel, D., 1998. Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. Cancer Res. 58, 2170-2175.
[12]	Berman, B.P., Weisenberger, D.J., Aman, J.F., Hinoue, T., Ramjan, Z., Liu, Y., Noushmehr, H., Lange, C.P.E., Van Dijk, C.M. et al., 2012. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear laminag-associated domains. Nat. Genet. 44, 40-46.
[13]	Bersani, F., Lee, E., Kharchenko, P.V., Xu, A.W., Liu, M., Xega, K., MacKenzie, O.C., Brannigan, B.W., Wittner, B.S., et al., 2015. Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer. Proc. Natl. Acad. Sci. U. S. A. 112, 15148-15153.
[14]	Bhaskara, S., Knutson, S.K., Jiang, G., Chandrasekharan, M.B., Wilson, A.J., Zheng, S., Yenamandra, A., Locke, K., Yuan, J.L. et al., 2010. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18, 436-447.
[15]	Bird, A., 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21.
[16]	Broers, J.L.V., Ramaekers, F.C.S., Bonne, G., Yaou, R.B., Hutchison, C.J., 2006. Nuclear lamins: Laminopathies and their role in premature ageing. Physiol. Rev. 86, 967-1008.
[17]	Bruckmann, N.H., Pedersen, C.B., Ditzel, H.J., Gjerstorff, M.F., 2018. Epigenetic reprogramming of pericentromeric satellite DNA in premalignant and malignant lesions. Mol. Cancer Res. 16, 417-427.
[18]	Brun, M.E., Ruault, M., Ventura, M., Roizes, G., De Sario, A., 2003. Juxtacentromeric region of human chromosome 21: a boundary between centromeric heterochromatin and euchromatic chromosome arms. Gene 312, 41-50.
[19]	Campagna, D., Romualdi, C., Vitulo, N., Del Favero, M., Lexa, M., Cannata, N., Valle, G., 2005. RAP: A new computer program for de novo identification of repeated sequences in whole genomes. Bioinformatics 21, 582-588.
[20]	Cappell, K.M., Sinnott, R., Taus, P., Maxfield, K., Scarbrough, M., Whitehurst, A.W., 2012. Multiple cancer testis antigens function to support tumor cell mitotic fidelity. Mol. Cell. Biol. 32, 4131-4140.
[21]	Chakravarthi, B.V.S.K., Nepal, S., Varambally, S., 2016. Genomic and epigenomic alterations in cancer. Am. J. Pathol. 186, 1724-1735.
[22]	Chang, J., Kim, N.G., Piao, Z., Park, C., Park, K.S., Paik, Y.K., Lee, W.J., Kim, B.R., Kim, H., 2002. Assessment of chromosomal losses and gains in hepatocellular carcinoma. Cancer Lett. 182, 193-202.
[23]	Collins, F.S., Patrinos, A., Jordan, E., Chakravarti, A., Gesteland, R., Walters, L.R., 1998. New goals for the U.S. Human Genome Project: 1998-2003. Science 282, 682-689.
[24]	Cruickshanks, H.A., McBryan, T., Nelson, D.M., Vanderkraats, N.D., Shah, P.P., Van Tuyn, J., Singh Rai, T., Brock, C., Donahue, G. et al., 2013. Senescent cells harbour features of the cancer epigenome. Nat. Cell Biol. 15, 1495-1506.
[25]	Dejardin, J., 2015. Switching between epigenetic states at pericentromeric heterochromatin. Trends Genet. 31, 661-672.
[26]	Dekker, J., Misteli, T., 2015. Long-range chromatin interactions. Cold Spring Harb. Perspect. Biol. 7, a019356.
[27]	Delcher, A.L., Kasif, S., Fleischmann, R.D., Peterson, J., White, O., Salzberg, S.L., 1999. Alignment of whole genomes. Nucleic Acids Res. 27, 2369-2376.
[28]	Dopp, E., Papp, T., Schiffmann, D., 1997. Detection of hyperdiploidy and chromosome breakage affecting the 1 (1cen-q12) region in lentigo malignant melanoma (LMM), superficial spreading melanoma (SSM) and congenital nevus (CN) cells in vitro by the multicolor FISH technique. Cancer Lett. 120, 157-163.
[29]	Dostie, J., Richmond, T.A., Arnaout, R.A., Selzer, R.R., Lee, W.L., Honan, T.A., Rubio, E.D., Krumm, A., Lamb, J. et al., 2006. Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements. Genome Res. 16, 1299-1309.
[30]	Du, J., Johnson, L.M., Jacobsen, S.E., Patel, D.J., 2015. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 16, 519-532.
[31]	Du, L., Zhou, H., Yan, H., 2007. OMWSA: Detection of DNA repeats using moving window spectral analysis. Bioinformatics 23, 631-633.
[32]	Edgar, R.C., Myers, E.W., 2005. PILER: Identification and classification of genomic repeats. Bioinformatics 21, i152-i158.
[33]	Edmunds, J.W., Mahadevan, L.C., Clayton, A.L., 2008. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 27, 406-420.
[34]	Ehrlich, M., 2009. DNA hypomethylation in cancer cells. Epigenomics 1, 239-259.
[35]	Ehrlich, M., Sanchez, C., Shao, C., Nishiyama, R., Kehrl, J., Kuick, R., Kubota, T., Hanash, S., 2008. ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation. Autoimmunity 41, 253-271.
[36]	Eichler, E.E., 1998. Masquerading Repeats: Paralogous Pitfalls of the Human Genome. Genome Res. 8, 758-762.
[37]	Eot-Houllier, G., Fulcrand, G., Watanabe, Y., Magnaghi-Jaulin, L., Jaulin, C., 2008. Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion. Genes Dev. 22, 2639-2644.
[38]	Erdel, F., Rippe, K., 2018. Formation of chromatin subcompartments by phase separation. Biophys. J. 114, 2262-2270.
[39]	Esteller, M., 2002. CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future. Oncogene 21, 5427-5440.
[40]	Fanelli, M., Caprodossi, S., Ricci-Vitiani, L., Porcellini, A., Tomassoni-Ardori, F., Amatori, S., Andreoni, F., Magnani, M., De Maria, R. et al., 2008. Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment. Oncogene 27, 358-365.
[41]	Fawcett, D.W., 1966. On the occurrence of a fibrous lamina on the inner aspect of the nuclear envelope in certain cells of vertebrates. Am. J. Anat. 119, 129-145.
[42]	Fischer, T., Cui, B., Dhakshnamoorthy, J., Zhou, M., Rubin, C., Zofall, M., Veenstra, T.D., Grewal, S.I.S., 2009. Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast. Proc. Natl. Acad. Sci. U. S. A. 106, 8998-9003.
[43]	Fodor, B.D., Shukeir, N., Reuter, G., Jenuwein, T., 2010. Mammalian su(var) genes in chromatin control. Annu. Rev. Cell Dev. Biol. 26, 471-501.
[44]	Fortna, A., Kim, Y., MacLaren, E., Marshall, K., Hahn, G., Meltesen, L., Brenton, M., Hink, R., Burgers, S. et al., 2004. Lineage-Specific Gene Duplication and Loss in Human and Great Ape Evolution. PLoS Biol. 2, e207.
[45]	Fournier, A., Florin, A., Lefebvre, C., Solly, F., Leroux, D., Callanan, M.B., 2007. Genetics and epigenetics of 1q rearrangements in hematological malignancies. Cytogenet. Genome Res. 118, 320-327.
[46]	Fraga, M.F., Ballestar, E., Villar-Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C., Ropero, S. et al., 2005. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet. 37, 391-400.
[47]	Fransz, P., de Jong, H., 2011. From nucleosome to chromosome: A dynamic organization of genetic information. Plant J. 66, 4-17.
[48]	Fransz, P., de Jong, J.H., Lysak, M., Castiglione, M.R., Schubert, I., 2002. Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate. Proc. Natl. Acad. Sci. U. S. A. 99, 14584-14589.
[49]	Frescas, D., Guardavaccaro, D., Kato, H., Poleshko, A., Katz, R.A., Pagano, M., 2008. KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state. Cell Cycle 7, 3539-3547.
[50]	Fullwood, M.J., Liu, M.H., Pan, Y.F., Liu, J., Xu, H., Mohamed, Y.B., Orlov, Y.L., Velkov, S., Ho, A. et al., 2009. An oestrogen-receptor-α-bound human chromatin interactome. Nature 462, 58-64.
[51]	Funabiki, H., Hagan, I., Uzawa, S., Yanagida, M., 1993. Cell cycle-dependent specific positioning and clustering of centromeres and telomeres in fission yeast. J. Cell Biol. 121, 961-976.
[52]	Ghafouri-Fard, S., 2012. Are cancer-testis antigens cancer stem sell markers? J. Sing. Cel Genom Proteomics 1, e104.
[53]	Gjerstorff, M.F., 2020. Novel insights into epigenetic reprogramming and destabilization of pericentromeric heterochromatin in cancer. Front. Oncol. 10, 594163.
[54]	Gjerstorff, M.F., Terp, M.G., Hansen, M.B., Ditzel, H.J., 2016. The role of GAGE cancer/testis antigen in metastasis: The jury is still out. BMC Cancer 16, 7.
[55]	Gladyshev, E., Kleckner, N., 2014. Direct recognition of homology between double helices of DNA in Neurospora crassa. Nat. Commun. 5, 3509.
[56]	Goldman, R.D., Gruenbaum, Y., Moir, R.D., Shumaker, D.K., Spann, T.P., 2002. Nuclear lamins: Building blocks of nuclear architecture. Genes Dev. 16, 533-547.
[57]	Gopalakrishnan, S., Sullivan, B.A., Trazzi, S., Della Valle, G., Robertson, K.D., 2009. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum. Mol. Genet. 18, 3178-3193.
[58]	Grunwald, C., Koslowski, M., Arsiray, T., Dhaene, K., Praet, M., Victor, A., Morresi-Hauf, A., Lindner, M., Passlick, B. et al., 2006. Expression of multiple epigenetically regulated cancer/germline genes in nonsmall cell lung cancer. Int. J. Cancer 118, 2522-2528.
[59]	Guelen, L., Pagie, L., Brasset, E., Meuleman, W., Faza, M.B., Talhout, W., Eussen, B.H., De Klein, A., Wessels, L. et al., 2008. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453, 948-951.
[60]	Guschanski, K., Warnefors, M., Kaessmann, H., 2017. The evolution of duplicate gene expression in mammalian organs. Genome Res. 27, 1461-1474.
[61]	Haaf, T., Schmid, M., 1991. Chromosome topology in mammalian interphase nuclei. Exp. Cell Res. 192, 325-332.
[62]	Hall, A.E., Kettler, G.C., Preuss, D., 2006. Dynamic evolution at pericentromeres. Genome Res. 16, 355-364.
[63]	Hall, L.L., Byron, M., Carone, D.M., Whitfield, T.W., Pouliot, G.P., Fischer, A., Jones, P., Lawrence, J.B., 2017. Demethylated HSATII DNA and HSATII RNA foci sequester PRC1 and MeCP2 into cancer-specific nuclear bodies. Cell Rep. 18, 2943-2956.
[64]	Han, J., Zhang, Z., Wang, K., 2018. 3C and 3C-based techniques: The powerful tools for spatial genome organization deciphering. Mol. Cytogenet. 11, 21.
[65]	Hanahan, D., Weinberg, R.A., 2011. Hallmarks of cancer: The next generation. Cell 144, 646-674.
[66]	Hansen, K.D., Timp, W., Bravo, H.C., Sabunciyan, S., Langmead, B., McDonald, O.G., Wen, B., Wu, H., Liu, Y. et al., 2011. Increased methylation variation in epigenetic domains across cancer types. Nat. Genet. 43, 768-775.
[67]	Healy, J., Thomas, E.E., Schwartz, J.T., Wigler, M., 2003. Annotating large genomes with exact word matches. Genome Res. 13, 2306-2315.
[68]	Hon, G.C., Hawkins, R.D., Caballero, O.L., Lo, C., Lister, R., Pelizzola, M., Valsesia, A., Ye, Z., Kuan, S. et al., 2012. Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Res. 22, 246-258.
[69]	Hughes, J.R., Roberts, N., Mcgowan, S., Hay, D., Giannoulatou, E., Lynch, M., De Gobbi, M., Taylor, S., Gibbons, R., Higgs, D.R., 2014. Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment. Nat. Genet. 46, 205-212.
[70]	Huo, X., Ji, L., Zhang, Y., Lv, P., Cao, X., Wang, Q., Yan, Z., Dong, S., Du, D. et al., 2020. The nuclear matrix protein SAFB cooperates with major satellite RNAs to stabilize heterochromatin architecture partially through phase separation. Mol. Cell 77, 368-383.e7.
[71]	Hyun, K., Jeon, J., Park, K., Kim, J., 2017. Writing, erasing and reading histone lysine methylations. Exp. Mol. Med. 49, e324.
[72]	Ikegami, K., Egelhofer, T.A., Strome, S., Lieb, J.D., 2010. Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2. Genome Biol. 11, R120.
[73]	Inoue, S., Sugiyama, S., Travers, A.A., Ohyama, T., 2007. Self-assembly of double-stranded DNA molecules at nanomolar concentrations. Biochemistry 46, 164-171.
[74]	Jachowicz, J.W., Santenard, A., Bender, A., Muller, J., Torres, M.E.P., 2013. Heterochromatin establishment at pericentromeres depends on nuclear position. Genes Dev. 27, 2427-2432.
[75]	Jacobs, S.A., Taverna, S.D., Zhang, Y., Briggs, S.D., Li, J., Eissenberg, J.C., Allis, C.D., Khorasanizadeh, S., 2001. Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J. 20, 5232-5241.
[76]	James, S.R., Cedeno, C.D., Sharma, A., Zhang, W., Mohler, J.L., Odunsi, K., Wilson, E.M., Karpf, A.R., 2013. DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11. Epigenetics 8, 849-863.
[77]	Ji, W., Hernandez, R., Zhang, X.Y., Qu, G.Z., Frady, A., Varela, M., Ehrlich, M., 1997. DNA demethylation and pericentromeric rearrangements of chromosome 1. Mutat. Res. 379, 33-41.
[78]	Jiang, Y.L., Rigolet, M., Bourc’his, D., Nigon, F., Bokesoy, I., Fryns, J.P., Hulten, M., Jonveaux, P., Maraschio, P. et al., 2005. DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Hum. Mutat. 25, 56-63.
[79]	Jiao, H.L., Ye, Y.P., Yang, R.W., Sun, H.Y., Wang, S.Y., Wang, Y.X., Xiao, Z.Y., He, L.Q., Cai, J.J. et al., 2017. Downregulation of SAFB sustains the NF-kB pathway by targeting TAK1 during the progression of colorectal cancer. Clin. Cancer Res. 23, 7108-7118.
[80]	Joergensen, S., Schotta, G., Soerensen, C.S., 2013. Histone H4 Lysine 20 methylation: Key player in epigenetic regulation of genomic integrity. Nucleic Acids Res. 41, 2797-2806.
[81]	Jurka, J., Klonowski, P., Dagman, V., Pelton, P., 1996. Censor - A program for identification and elimination of repetitive elements from DNA sequences. Comput. Chem. 20, 119-121.
[82]	Kang, Z.J., Liu, Y.F., Xu, L.Z., Long, Z.J., Huang, D., Yang, Y., Liu, B., Feng, J.X., Pan, Y.J. et al., 2016. The Philadelphia chromosome in leukemogenesis. Chin. J. Cancer 35, 48.
[83]	Khalil, A.M., Driscoll, D.J., 2010. Epigenetic regulation of pericentromeric heterochromatin during mammalian meiosis. Cytogenet. Genome Res. 129, 280-289.
[84]	Kim, H.J., Yardimci, G.G., Bonora, G., Ramani, V., Liu, J., Qiu, R., Lee, C., Hesson, J., Ware, C.B. et al., 2020. Capturing cell type-specific chromatin compartment patterns by applying topic modeling to single-cell Hi-C data. PLOS Comput. Biol. 16, e1008173.
[85]	Kind, J., Pagie, L., Ortabozkoyun, H., Boyle, S., De Vries, S.S., Janssen, H., Amendola, M., Nolen, L.D., Bickmore, W.A., Van Steensel, B., 2013. Single-cell dynamics of genome-nuclear lamina interactions. Cell 153, 178-192.
[86]	Kishikawa, T., Otsuka, M., Yoshikawa, T., Ohno, M., Ijichi, H., Koike, K., 2016. Satellite RNAs promote pancreatic oncogenic processes via the dysfunction of YBX1. Nat. Commun. 7, 13006.
[87]	Krumm, A., Duan, Z., 2019. Understanding the 3D genome: Emerging impacts on human disease. Semin. Cell Dev. Biol. 90, 62-77.
[88]	Kuo, L.J., Yang, L.X., 2008. γ-H2AX- A novel biomaker for DNA double-strand breaks. In Vivo 22, 305-310.
[89]	Kurtz, S., Narechania, A., Stein, J.C., Ware, D., 2008. A new method to compute K-mer frequencies and its application to annotate large repetitive plant genomes. BMC Genomics 9, 517.
[90]	Kurtz, S., Schleiermacher, C., 1999. REPuter: Fast computation of maximal repeats in complete genomes. Bioinformatics 15, 426-427.
[91]	Lachner, M., O’Carroll, D., Rea, S., Mechtler, K., Jenuwein, T., 2001. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116-120.
[92]	Lanctot, C., Cheutin, T., Cremer, M., Cavalli, G., Cremer, T., 2007. Dynamic genome architecture in the nuclear space: Regulation of gene expression in three dimensions. Nat. Rev. Genet. 8, 104-115.
[93]	Larson, A.G., Elnatan, D., Keenen, M.M., Trnka, M.J., Johnston, J.B., Burlingame, A.L., Agard, D.A., Redding, S., Narlikar, G.J., 2017. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236-240.
[94]	Lee, Y.C.G., Ogiyama, Y., Martins, N.M.C., Beliveau, B.J., Acevedo, D., Wu, C.T., Cavalli, G., Karpen, G.H., 2020. Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin. PLoS Genet. 16, e1008673.
[95]	Lefebvre, A., Lecroq, T., Dauchel, H., Alexandre, J., 2003. FORRepeats: Detects repeats on entire chromosomes and between genomes. Bioinformatics 19, 319-326.
[96]	Li, R., Ye, J., Li, S., Wang, J., Han, Y., Ye, C., Wang, J., Yang, H., Yu, J. et al., 2005. ReAS: Recovery of ancestral sequences for transposable elements from the unassembled reads of a whole genome shotgun. PLoS Comput. Biol. 1, e43.
[97]	Lin, Y., Protter, D.S.W., Rosen, M.K., Parker, R., 2015. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60, 208-219.
[98]	Liu, T., Wang, Z., 2018. Reconstructing high-resolution chromosome three-dimensional structures by Hi-C complex networks. BMC Bioinformatics 19, 496.
[99]	Loyola, A., Tagami, H., Bonaldi, T., Roche, D., Quivy, J.P., Imhof, A., Nakatani, Y., Dent, S.Y.R., Almouzni, G., 2009. The HP1α-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep. 10, 769-775.
[100]	Ma, W., Ay, F., Lee, C., Gulsoy, G., Deng, X., Cook, S., Hesson, J., Cavanaugh, C., Ware, C.B. et al., 2018. Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution. Methods 142, 59-73.
[101]	Marchio, A., Meddeb, H., Pineau, P., Danglot, G., Tiollais, P., Bernheim, A., Dejean, A., 1997. Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosom. Cancer 18, 59-65.
[102]	Mayer, R., Brero, A., Von Hase, J., Schroeder, T., Cremer, T., Dietzel, S., 2005. Common themes and cell type specific variations of higher order chromatin arrangements in the mouse. BMC Cell Biol. 6, 44.
[103]	McCarthy, E.M., McDonald, J.F., 2003. LTR STRUC: A novel search and identification program for LTR retrotransposons. Bioinformatics 19, 362-367.
[104]	Mertens, F., Johansson, B., Hoglund, M., Mitelman, F., 1997. Chromosomal imbalance maps of malignant solid tumors: A cytogenetic survey of 3185 neoplasms. Cancer Res. 57, 2765-2780.
[105]	Meuleman, W., Peric-Hupkes, D., Kind, J., Beaudry, J.B., Pagie, L., Kellis, M., Reinders, M., Wessels, L., Van Steensel, B., 2013. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Res. 23, 270-280.
[106]	Mudge, J.M., Jackson, M.S., 2005. Evolutionary implications of pericentromeric gene expression in humans. Cytogenet. Genome Res. 108, 47-57.
[107]	Mukhopadhyay, N.K., Kim, J., You, S., Morello, M., Hager, M.H., Huang, W.C., Ramachandran, A., Yang, J., Cinar, B. et al., 2014. Scaffold attachment factor B1 regulates the androgen receptor in concert with the growth inhibitory kinase MST1 and the methyltransferase EZH2. Oncogene 33, 3235-3245.
[108]	Muller-Ott, K., Erdel, F., Matveeva, A., Mallm, J., Rademacher, A., Hahn, M., Bauer, C., Zhang, Q., Kaltofen, S. et al., 2014. Specificity, propagation, and memory of pericentric heterochromatin. Mol. Syst. Biol. 10, 746.
[109]	Narayan, A., Ji, W., Zhang, X.Y., Marrogi, A., Graff, J.R., Baylin, S.B., Ehrlich, M., 1998. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int. J. Cancer 77, 833-838.
[110]	Natsume, A., Wakabayashi, T., Tsujimura, K., Shimato, S., Ito, M., Kuzushima, K., Kondo, Y., Sekido, Y., Kawatsura, H. et al., 2008. The DNA demethylating agent 5-aza-2′-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int. J. Cancer 122, 2542-2553.
[111]	Nishikawa, J.I., Ohyama, T., 2013. Selective association between nucleosomes with identical DNA sequences. Nucleic Acids Res. 41, 1544-1554.
[112]	Norman, M., Rivers, C., Lee, Y.B., Idris, J., Uney, J., 2016. The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins. Biochem. J. 473, 4271-4288.
[113]	Nozawa, R.S., Yamamoto, T., Takahashi, M., Tachiwana, H., Maruyama, R., Hirota, T., Saitoh, N., 2020. Nuclear microenvironment in cancer: Control through liquid-liquid phase separation. Cancer Sci. 111, 3155-3163.
[114]	Oesterreich, S., Allredl, D.C., Mohsin, S.K., Zhang, Q., Wong, H., Lee, A.V., Osborne, C.K., O’Connell, P., 2001. High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer. Br. J. Cancer 84, 493-498.
[115]	Pandis, N., Jin, Y., Gorunova, L., Petersson, C., Bardi, G., Idvall, I., Johansson, B., Ingvar, C., Mandahl, N. et al., 1995. Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups. Genes, Chromosom. Cancer 12, 173-185.
[116]	Patel, A., Dharmarajan, V., Vought, V.E., Cosgrove, M.S., 2009. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J. Biol. Chem. 284, 24242-24256.
[117]	Peric-Hupkes, D., Meuleman, W., Pagie, L., Bruggeman, S.W.M., Solovei, I., Brugman, W., Graf, S., Flicek, P., Kerkhoven, R.M. et al., 2010. Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol. Cell 38, 603-613.
[118]	Pickersgill, H., Kalverda, B., De Wit, E., Talhout, W., Fornerod, M., Van Steensel, B., 2006. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat. Genet. 38, 1005-1014.
[119]	Pinheiro, I., Margueron, R., Shukeir, N., Eisold, M., Fritzsch, C., Richter, F.M., Mittler, G., Genoud, C., Goyama, S. et al., 2012. Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150, 948-960.
[120]	Prada, D., Gonzalez, R., Sanchez, L., Castro, C., Fabian, E., Herrera, L.A., 2012. Satellite 2 demethylation induced by 5-azacytidine is associated with missegregation of chromosomes 1 and 16 in human somatic cells. Mutat. Res. 729, 100-105.
[121]	Price, A.L., Jones, N.C., Pevzner, P.A., 2005. De novo identification of repeat families in large genomes. Bioinformatics 21, i351-i358.
[122]	Ragoczy, T., Telling, A., Scalzo, D., Kooperberg, C., Groudine, M., 2014. Functional redundancy in the nuclear compartmentalization of the Late-Replicating genome. Nucleus 5, 626-635.
[123]	Reddy, K.L., Feinberg, A.P., 2013. Higher order chromatin organization in cancer. Semin. Cancer Biol. 23, 109-115.
[124]	RepeatMasker Home Page, 1997. http://www.repeatmasker.org/ (accessed 11.12.20).
[125]	Robson, M.I., de las Heras, J.I., Czapiewski, R., Le Thanh, P., Booth, D.G., Kelly, D.A., Webb, S., Kerr, A.R.W., Schirmer, E.C., 2016. Tissue-specific gene repositioning by muscle nuclear membrane proteins enhances repression of critical developmental genes during myogenesis. Mol. Cell 62, 834-847.
[126]	Sakaguchi, A., Karachentsev, D., Seth-Pasricha, M., Druzhinina, M., Steward, R., 2008. Functional characterization of the drosophila Hmt4-20/Suv4-20 histone methyltransferase. Genetics 179, 317-322.
[127]	Saksouk, N., Simboeck, E., Dejardin, J., 2015. Constitutive heterochromatin formation and transcription in mammals. Epigenetics Chromatin 8, 3.
[128]	Sanders, S.L., Portoso, M., Mata, J., Bahler, J., Allshire, R.C., Kouzarides, T., 2004. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119, 603-614.
[129]	Saurin, A.J., Shiels, C., Williamson, J., Satijn, D.P.E., Otte, A.P., Sheer, D., Freemont, P.S., 1998. The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain. J. Cell Biol. 142, 887-898.
[130]	Sawyer, J.R., Tian, E., Walker, B.A., Wardell, C., Lukacs, J.L., Sammartino, G., Bailey, C., Schinke, C.D., Thanendrarajan, S. et al., 2019. An acquired high-risk chromosome instability phenotype in multiple myeloma: Jumping 1q Syndrome. Blood Cancer J. 9, 62.
[131]	Sawyer, J.R., Tricot, G., Mattox, S., Jagannath, S., Barlogie, B., 1998. Jumping translocations of chromosome 1q in multiple myeloma: Evidence for a mechanism involving decondensation of pericentromeric heterochromatin. Blood 91, 1732-1741.
[132]	Schotta, G., Lachner, M., Sarma, K., Ebert, A., Sengupta, R., Reuter, G., Reinberg, D., Jenuwein, T., 2004. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 18, 1251-1262.
[133]	Schotta, G., Sengupta, R., Kubicek, S., Malin, S., Kauer, M., Callen, E., Celeste, A., Pagani, M., Opravil, S. et al., 2008. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev. 22, 2048-2061.
[134]	Shah, P.P., Donahue, G., Otte, G.L., Capell, B.C., Nelson, D.M., Cao, K., Aggarwala, V., Cruickshanks, H.A., Rai, T.S. et al., 2013. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 27, 1787-1799.
[135]	Shang, W.H., Hori, T., Westhorpe, F.G., Godek, K.M., Toyoda, A., Misu, S., Monma, N., Ikeo, K., Carroll, C.W. et al., 2016. Acetylation of histone H4 lysine 5 and 12 is required for CENP-A deposition into centromeres. Nat. Commun. 7, 13465.
[136]	Sharma, A., Albahrani, M., Zhang, W., Kufel, C.N., James, S.R., Odunsi, K., Klinkebiel, D., Karpf, A.R., 2019. Epigenetic activation of POTE genes in ovarian cancer. Epigenetics 14, 185-197.
[137]	Sharma, D., Issac, B., Raghava, G.P.S., Ramaswamy, R., 2004. Spectral repeat finders (SRF): Identification of repetitive sequences using Fourier transformation. Bioinformatics 20, 1405-1412.
[138]	Shumaker, D.K., Kuczmarski, E.R., Goldman, R.D., 2003. The nucleoskeleton: Lamins and actin are major players in essential nuclear functions. Curr. Opin. Cell Biol. 15, 358-366.
[139]	Shvachko, L.P., 2008. Alterations of constitutive pericentromeric heterochromatin in lymphocytes of cancer patients and lymphocytes exposed to 5-azacytidine is associated with DNA-hypomethylation. Exp. Oncol. 30, 230-234.
[140]	Singh, A., Gupta, S., Sachan, M., 2019. Epigenetic biomarkers in the management of ovarian cancer: Current prospectives. Front. Cell Dev. Biol. 7, 182.
[141]	Slee, R.B., Steiner, C.M., Herbert, B.S., Vance, G.H., Hickey, R.J., Schwarz, T., Christan, S., Radovich, M., Schneider, B.P. et al., 2012. Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. Oncogene 31, 3244-3253.
[142]	Smurova, K., De Wulf, P., 2018. Centromere and pericentromere transcription: Roles and regulation … in sickness and in health. Front. Genet. 9, 674.
[143]	Solovei, I., Schermelleh, L., During, K., Engelhardt, A., Stein, S., Cremer, C., Cremer, T., 2004. Differences in centromere positioning of cycling and postmitotic human cell types. Chromosoma 112, 410-423.
[144]	Soltanian, S., Dehghani, H., 2018. BORIS: A key regulator of cancer stemness. Cancer Cell Int. 18, 154.
[145]	Stancheva, I., 2005. Caught in conspiracy : cooperation between DNA methylation and histone H3K9 methylation. Cell 83, 385-395.
[146]	Strom, A.R., Emelyanov, A.V., Mir, M., Fyodorov, D.V., Darzacq, X., Karpen, G.H., 2017. Phase separation drives heterochromatin domain formation. Nature 547, 241-245.
[147]	Tachibana, M., Sugimoto, K., Fukushima, T., Shinkai, Y., 2001. SET domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J. Biol. Chem. 276, 25309-25317.
[148]	Tang, S.J., 2012. A model of repetitive-DNA-organized chromatin network of interphase chromosomes. Genes (Basel) 3, 167-175.
[149]	Tang, S.J., 2011a. A model of DNA repeat-assembled mitotic chromosomal skeleton. Genes (Basel) 2, 661-670.
[150]	Tang, S.J., 2011b. Chromatin organization by repetitive elements (CORE): A genomic principle for the higher-order structure of chromosomes. Genes (Basel) 2, 502-515.
[151]	Tasselli, L., Xi, Y., Zheng, W., Tennen, R.I., Odrowaz, Z., Simeoni, F., Li, W., Chua, K.F., 2016. SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence. Nat. Struct. Mol. Biol. 23, 434-440.
[152]	Tessier, L.D., Dupont, C., Guimiot, F., Perrin, L., Marey, I., Smiljkovski, D., Le Tessier, D., Lebugle, C., Baumann, C. et al., 2012. 3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome. Clin. Genet. 82, 187-192.
[153]	Ting, D.T., Lipson, D., Paul, S., Brannigan, B.W., Akhavanfard, S., Coffman, E.J., Contino, G., Deshpande, V., Iafrate, A.J. et al., 2011. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331, 593-596.
[154]	Toth, G., Deak, G., Barta, E., Kiss, G.B., 2006. PLOTREP: A web tool for defragmentation and visual analysis of dispersed genomic repeats. Nucleic Acids Res. 34, W708-W713.
[155]	Traynor, S., Moellegaard, N.E., Joergensen, M.G., Bruckmann, N.H., Pedersen, C.B., Terp, M.G., Johansen, S., Dejardin, J., Ditzel, H.J., Gjerstorff, M.F., 2019. Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins. Nucleic Acids Res. 47, 6668-6684.
[156]	Tsuda, H., Takarabe, T., Kanai, Y., Fukutomi, T., Hirohashi, S., 2002. Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of chromosomes 16 and 1 with histological features and chromosomal abnormalities of human breast carcinomas. Am. J. Pathol. 161, 859-866.
[157]	Tu, Z., 2001. Eight novel families of miniature inverted repeat transposable elements in the African malaria mosquito, Anopheles gambiae. Proc. Natl. Acad. Sci. U. S. A. 98, 1699-1704.
[158]	Van Der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van Den Eynde, B., Knuth, A., Boon, T., 1991. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643-1647.
[159]	Van Koningsbruggen, S., Gierlinski, M., Schofield, P., Martin, D., Barton, G.J., Ariyurek, Y., Den Dunnen, J.T., Lamond, A.I., 2010. High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli. Mol. Biol. Cell 21, 3735-3748.
[160]	van Steensel, B., Belmont, A.S., 2017. Lamina-associated domains: Links with chromosome architecture, heterochromatin, and gene repression. Cell 169, 780-791.
[161]	Vaquero, A., Scher, M., Erdjument-Bromage, H., Tempst, P., Serrano, L., Reinberg, D., 2007a. SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. Nature 450, 440-444.
[162]	Vaquero, A., Sternglanz, R., Reinberg, D., 2007b. NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs. Oncogene 26, 5505-5520.
[163]	Vogel, M.J., Peric-Hupkes, D., van Steensel, B., 2007. Detection of in vivo protein - DNA interactions using DamID in mammalian cells. Nat. Protoc. 2, 1467-1478.
[164]	Wachsmuth, M., Caudron-Herger, M., Rippe, K., 2008. Genome organization: Balancing stability and plasticity. Biochim. Biophys. Acta - Mol. Cell Res. 1783, 2061-2079.
[165]	Walton, E., Francastel, C., Velasco, G., 2014. Dnmt3b prefers germ line genes and centromeric regions: Lessons from the ICF syndrome and cancer and implications for diseases. Biology (Basel). 3, 578-605.
[166]	Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G. et al., 2006. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125, 467-481.
[167]	Wijchers, P.J., Geeven, G., Eyres, M., Bergsma, A.J., Janssen, M., Verstegen, M., Zhu, Y., Schell, Y., Vermeulen, C. et al., 2015. Characterization and dynamics of pericentromere-associated domains in mice. Genome Res. 25, 958-969.
[168]	Wiles, E.T., Selker, E.U., 2017. H3K27 methylation: a promiscuous repressive chromatin mark. Curr. Opin. Genet. Dev. 43, 31-37.
[169]	Wong, N., Lai, P., Lee, S.W., Fan, S., Pang, E., Liew, C.T., Sheng, Z., Lau, J.W.Y., Johnson, P.J., 1999. Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: Relationship to disease stage, tumor size, and cirrhosis. Am. J. Pathol. 154, 37-43.
[170]	Wong, N., Lam, W.C., Lai, P.B.S., Pang, E., Lau, W.Y., Johnson, P.J., 2001. Hypomethylation of chromosome 1 heterochromatin DNA correlates with q-arm copy gain in human hepatocellular carcinoma. Am. J. Pathol. 159, 465-471.
[171]	Wu, H., Chen, X., Xiong, J., Li, Y., Li, H., Ding, X., Liu, S., Chen, S., Gao, S., Zhu, B., 2011. Histone methyltransferase G9a contributes to H3K27 methylation in vivo. Cell Res. 21, 365-367.
[172]	Wu, P., Li, T., Li, R., Jia, L., Zhu, P., Liu, Y., Chen, Q., Tang, D., Yu, Y., Li, C., 2017. 3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations. Nat. Commun. 8, 1937.
[173]	Wu, T.P., Wang, T., Seetin, M.G., Lai, Y., Zhu, S., Lin, K., Liu, Y., Byrum, S.D., Mackintosh, S.G. et al., 2016. DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 532, 329-333.
[174]	Xiang, S., Kato, M., Wu, L.C., Lin, Y., Ding, M., Zhang, Y., Yu, Y., McKnight, S.L., 2015. The LC domain of hnRNPA2 adopts similar conformations in hydrogel polymers, Liquid-like droplets, and nuclei. Cell 163, 829-839.
[175]	Yamada, R., Takahashi, A., Torigoe, T., Morita, R., Tamura, Y., Tsukahara, T., Kanaseki, T., Kubo, T., Watarai, K. et al., 2013. Preferential expression of cancer/testis genes in cancer stem-like cells: Proposal of a novel sub-category, cancer/testis/stem gene. Tissue Antigens 81, 428-434.
[176]	Yamada, T., Fischle, W., Sugiyama, T., Allis, C.D., Grewal, S.I.S., 2005. The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol. Cell 20, 173-185.
[177]	Yang, G., Hall, T.C., 2003. MAK, a computational tool kit for automated MITE analysis. Nucleic Acids Res. 31, 3659-3665.
[178]	Yang, M., Vesterlund, M., Siavelis, I., Moura-Castro, L.H., Castor, A., Fioretos, T., Jafari, R., Lilljebjorn, H., Odom, D.T. et al., 2019. Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia. Nat. Commun. 10, 1519.
[179]	Zaidi, S.K., Young, D.W., Javed, A., Pratap, J., Montecino, M., Van Wijnen, A., Lian, J.B., Stein, J.L., Stein, G.S., 2007. Nuclear microenvironments in biological control and cancer. Nat. Rev. Cancer 7, 454-463.
[180]	Zhang, P., Spradling, A.C., 1995. The Drosophila salivary gland chromocenter contains highly polytenized subdomains of mitotic heterochromatin. Genetics 139, 659-670.
[181]	Zhang, W., Xu, J., 2017. DNA methyltransferases and their roles in tumorigenesis. Biomark. Res. 5, 1.