Journal of Genetics and Genomics

PDGF signaling from pharyngeal pouches promotes arch artery morphogenesis

Aihua Mao, Mingming Zhang, Jie Liu, Yu Cao, Qiang Wang

2019, 46(12): 551-559. doi: 10.1016/j.jgg.2019.11.004

Abstract (98) HTML PDF (1)

Abstract:
The great vessels of the heart originate from the pharyngeal arch arteries (PAAs). Anomalies of the PAAs often occur together with pharyngeal pouch malformations, but the reasons for this phenomenon are not fully understood. In the current study, we show that platelet-derived growth factor (PDGF) signaling derived from the pharyngeal pouches plays an important function in PAA vasculogenesis. During PAA development in zebrafish embryos, pdgfαa and pdgfαb are expressed in the developing pharyngeal pouches. Results from loss-of-function experiments revealed a critical role of these genes in PAA formation. We found that nitroreductase (NTR)-mediated pouch ablation distinctly decreased PDGF receptor tyrosine phosphorylation, yielding a severe loss of PAAs. Importantly, pouch-specific overexpression of pdgfαa in pdgfαa; pdgfαb mutants significantly relieved the PAA defects, which indicated a primary role of pharyngeal pouch-expressed PDGF ligands in signal activation and PAA morphogenesis. Our findings further showed that PDGF signaling was indispensable for the proliferation of PAA angioblasts. Together, these results established a role for PDGFαa- and PDGFαb-mediated tissue-tissue interaction during PAA development.

Glycolysis regulates gene expression by promoting the crosstalk between H3K4 trimethylation and H3K14 acetylation in Saccharomyces cerevisiae

Yinsheng Wu, Shihao Zhang, Xuanyunjing Gong, Qi Yu, Yuan Zhang, Mingdan Luo, Xianhua Zhang, Jerry L. Workman, Xilan Yu, Shanshan Li

2019, 46(12): 561-574. doi: 10.1016/j.jgg.2019.11.007

Abstract (122) HTML PDF (2)

Abstract:
Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth. However, how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown. Here, we report that glucose specifically induces histone H3K4 trimethylation (H3K4me3), an evolutionarily conserved histone covalent modification associated with active gene transcription, and that glycolytic enzymes and metabolites are required for this induction. Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Set1 to catalyze H3K4me3, glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation. Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14, which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3. By repressing Jhd2-mediated H3K4 demethylation, glycolytic enzymes regulate gene expression and cell survival during chronological aging. Thus, our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.

MpbR, an essential transcriptional factor for Mycobacterium tuberculosis survival in the host, modulates PIM biosynthesis and reduces innate immune responses

Yugang Li, Weihui Li, Zhiwei Xie, Hui Xu, Zheng-Guo He

2019, 46(12): 575-589. doi: 10.1016/j.jgg.2019.12.002

Abstract (131) HTML PDF (2)

Abstract:
Mycobacterium tuberculosis possesses unique cellular envelope components that contribute to bacterial escape from host immune surveillance. Phosphatidylinositol mannosides (PIMs) and their higher derivatives are important molecules implicated in host-pathogen interactions in the course of tuberculosis. However, the biosynthetic regulation of these specific lipids and its effect on the bacterial fate in the infected host remain unclear. Here, we show that a hypothetical M. tuberculosis transcriptional factor designated as MpbR negatively regulates two transporter genes and affects mycobacterial PIM biosynthesis and biofilm formation. MpbR inhibits the accumulation of acylated PIM lipids and triggers the mycobacterium to reduce the production of reactive oxygen species and NO during infection, which enhances the survival ofM. tuberculosis in macrophages. MpbR deletion reduces M. tuberculosis lung burdens and inflammation of infected mice. These findings provide new insights into the regulation of mycobacterial lipid metabolism and its correlation with pathogenesis of M. tuberculosis.

Disruptor of telomeric silencing 1-like (DOT1L) is involved in breast cancer metastasis via transcriptional regulation of MALAT1 and ZEB2

Yang Duan, Xingyan Zhang, Lihong Yang, Xu Dong, Zhanye Zheng, Yiming Cheng, Hao Chen, Bei Lan, Dengwen Li, Jun Zhou, Chenghao Xuan

2019, 46(12): 591-594. doi: 10.1016/j.jgg.2019.11.008

Abstract (81) HTML PDF (3)

Abstract:

dbEMT 2.0: An updated database for epithelial-mesenchymal transition genes with experimentally verified information and precalculated regulation information for cancer metastasis

Min Zhao, Yining Liu, Chong Zheng, Hong Qu

2019, 46(12): 595-597. doi: 10.1016/j.jgg.2019.11.010

Abstract (146) HTML PDF (4)

Abstract:

A behavioral paradigm to study the persistence of reward memory extinction in Drosophila

Lingling Wang, Qi Yang, Binyan Lu, Lianzhang Wang, Yi Zhong, Qian Li

2019, 46(12): 599-601. doi: 10.1016/j.jgg.2019.11.001

Abstract (77) HTML PDF (1)

Abstract:

2019 Vol. 46, No. 12