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肾脏发育的表观遗传调控。

Epigenetic regulation of renal development.

机构信息

Tulane University School of Medicine, 1430 Tulane Avenue, Department of Pediatrics, Section of Pediatric Nephrology, New Orleans, LA, 70112, USA.

出版信息

Semin Cell Dev Biol. 2019 Jul;91:111-118. doi: 10.1016/j.semcdb.2018.08.014. Epub 2018 Sep 5.

Abstract

Developmental changes in cell fate are tightly regulated by cell-type specific transcription factors. Chromatin reorganization during organismal development ensures dynamic access of developmental regulators to their cognate DNA sequences. Thus, understanding the epigenomic states of promoters and enhancers is of key importance. Recent years have witnessed significant advances in our knowledge of the transcriptional mechanisms of kidney development. Emerging evidence suggests that histone deacetylation by class I HDACs and H3 methylation on lysines 4, 27 and 79 play important roles in regulation of early and late gene expression in the developing kidney. Equally exciting is the realization that nephrogenesis genes in mesenchymal nephron progenitors harbor bivalent chromatin domains which resolve upon differentiation implicating chromatin bivalency in developmental control of gene expression. Here, we review current knowledge of the epigenomic states of nephric cells and current techniques used to study the dynamic chromatin states. These technological advances will provide an unprecedented view of the enhancer landscape during cell fate commitment and help in defining the complex transcriptional networks governing kidney development and disease.

摘要

细胞命运的发育变化受到细胞类型特异性转录因子的严格调控。在生物体发育过程中,染色质的重排确保了发育调节剂能够动态地与它们的同源 DNA 序列结合。因此,了解启动子和增强子的表观基因组状态至关重要。近年来,我们对肾脏发育的转录机制有了更深入的了解。新出现的证据表明,I 类组蛋白去乙酰化酶和组蛋白 H3 赖氨酸 4、27 和 79 的甲基化在调节发育中肾脏的早期和晚期基因表达中发挥着重要作用。同样令人兴奋的是,人们意识到间充质肾祖细胞中的肾发生基因具有二价染色质结构域,这些结构域在分化时会发生解聚,这表明染色质的二价性参与了基因表达的发育调控。在这里,我们回顾了肾细胞的表观基因组状态的现有知识,以及目前用于研究动态染色质状态的技术。这些技术进步将提供在细胞命运决定过程中增强子景观的空前视角,并有助于确定控制肾脏发育和疾病的复杂转录网络。

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