Journal of Genetics and Genomics

Epigenetics(-omics) Takes Center Stage

Jingde Zhu

2013, 40(7): 323-324. doi: 10.1016/j.jgg.2013.06.006

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Abstract:

Epigenetic Regulation of Serotonin Transporter in Psychiatric Disorders

Hiroko Sugawara, Miki Bundo, Jun Ishigooka, Kazuya Iwamoto, Tadafumi Kato

2013, 40(7): 325-329. doi: 10.1016/j.jgg.2012.10.002

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Abstract:

DNA Methylation, Behavior and Early Life Adversity

Moshe Szyf

2013, 40(7): 331-338. doi: 10.1016/j.jgg.2013.06.004

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Abstract:
The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene–environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome? DNA methylation is an enzymatically-catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.

The Epigenetic Switches for Neural Development and Psychiatric Disorders

Jingwen Lv, Yongjuan Xin, Wenhao Zhou, Zilong Qiu

2013, 40(7): 339-346. doi: 10.1016/j.jgg.2013.04.007

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Abstract:
The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted.

The Class III Histone Deacetylase Sirtuin 1 in Immune Suppression and Its Therapeutic Potential in Rheumatoid Arthritis

Sinyi Kong, Pricilla Yeung, Deyu Fang

2013, 40(7): 347-354. doi: 10.1016/j.jgg.2013.04.001

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Abstract:
Rheumatoid arthritis (RA) is a chronic debilitating disease of the joints. Both the innate and adaptive immune responses participate in the development and progression of RA. While several therapeutic reagents, such as TNF-α agonists, have been successfully developed for the clinical use in the treatment of RA, more than half of the patients do not respond to anti-TNF therapy. Therefore, new therapeutic reagents are needed. Recent studies have shown that sirtuin 1 (Sirt1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, is a critical negative regulator of both the innate and adaptive immune response in mice, and its altered functions are likely to be involved in autoimmune diseases. Small molecules that modulate Sirt1 functions are potential therapeutic reagents for autoimmune inflammatory diseases. This review highlights the role of Sirt1 in immune regulation and RA.

Histone Variants in Development and Diseases

Ping Chen, Jicheng Zhao, Guohong Li

2013, 40(7): 355-365. doi: 10.1016/j.jgg.2013.05.001

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Abstract:
Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled deposition, different histone variants have evolved distinct regulatory mechanisms for their expression, deposition and functional implications. The diversity of histone variants results in structural plasticity of chromatin and highlights functionally distinct chromosomal domain, which plays critical roles in development from a fertilized egg into a complex organism, as well as in aging and diseases. However, the mechanisms of this fundamental process are poorly understood so far. It is of particular interest to investigate how the variants are incorporated into chromatin and mark specific chromatin states to regulate gene expression, and how they are involved in development and diseases. In this review, we focus on recent progress in studies of epigenetic regulation of three extensively investigated variants including H2A.Z, macroH2A and H3.3, and their functional implications in development and diseases.

Regulatory Roles of Metabolites in Cell Signaling Networks

Feng Li, Wei Xu, Shimin Zhao

2013, 40(7): 367-374. doi: 10.1016/j.jgg.2013.05.002

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Abstract:
Mounting evidence suggests that cellular metabolites, in addition to being sources of fuel and macromolecular substrates, are actively involved in signaling and epigenetic regulation. Many metabolites, such as cyclic AMP, which regulates phosphorylation/dephosphorylation, have been identified to modulate DNA and histone methylation and protein stability. Metabolite-driven cellular regulation occurs through two distinct mechanisms: proteins allosterically bind or serve as substrates for protein signaling pathways, and metabolites covalently modify proteins to regulate their functions. Such novel protein metabolites include fumarate, succinyl-CoA, propionyl-CoA, butyryl-CoA and crontonyl-CoA. Other metabolites, including α-ketoglutarate, succinate and fumarate, regulate epigenetic processes and cell signaling via protein binding. Here, we summarize recent progress in metabolite-derived post-translational protein modification and metabolite-binding associated signaling regulation. Uncovering metabolites upstream of cell signaling and epigenetic networks permits the linkage of metabolic disorders and human diseases, and suggests that metabolite modulation may be a strategy for innovative therapeutics and disease prevention techniques.

2013 Vol. 40, No. 7