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The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes
Clinical Epigenetics ( IF 5.7 ) Pub Date : 2021-07-08 , DOI: 10.1186/s13148-021-01126-1
Tasnim H Beacon 1, 2 , Geneviève P Delcuve 2 , Camila López 1, 2 , Gino Nardocci 3, 4 , Igor Kovalchuk 5 , Andre J van Wijnen 6, 7 , James R Davie 1, 2
Affiliation  

Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark is typically restricted to narrow regions at the 5`end of the gene body, though a small subset of genes have a broad H3K4me3 domain which extensively covers the coding region. Although most studies focus on the H3K4me3 mark, the broad H3K4me3 domain is associated with a plethora of histone modifications (e.g., H3 acetylated at K27) and is therein termed broad epigenetic domain. Genes marked with the broad epigenetic domain are involved in cell identity and essential cell functions and have clinical potential as biomarkers for patient stratification. Reducing expression of genes with the broad epigenetic domain may increase the metastatic potential of cancer cells. Enhancers and super-enhancers interact with the broad epigenetic domain marked genes forming a hub of interactions involving nucleosome-depleted regions. Together, the regulatory elements coalesce with transcription factors, chromatin modifying/remodeling enzymes, coactivators, and the Mediator and/or Integrator complex into a transcription factory which may be analogous to a liquid–liquid phase-separated condensate. The broad epigenetic domain has a dynamic chromatin structure which supports frequent transcription bursts. In this review, we present the current knowledge of broad epigenetic domains.

中文翻译:

动态广泛的表观遗传(H3K4me3,H3K27ac)域作为必需基因的标记

转录活性染色质的标志是组蛋白 H3 在位于第一个外显子之后和转录起始位点周围的赖氨酸 4 (H3K4me3) 处发生三甲基化。这种表观遗传标记通常仅限于基因体 5' 端的狭窄区域,尽管一小部分基因具有广泛覆盖编码区域的广泛 H3K4me3 结构域。尽管大多数研究都集中在 H3K4me3 标记上,但广泛的 H3K4me3 结构域与过多的组蛋白修饰(例如,在 K27 处乙酰化的 H3)相关,并且在其中被称为广泛的表观遗传结构域。标记有广泛表观遗传结构域的基因涉及细胞特性和基本细胞功能,并具有作为患者分层生物标志物的临床潜力。减少具有广泛表观遗传结构域的基因表达可能会增加癌细胞的转移潜能。增强子和超级增强子与广泛的表观遗传域标记基因相互作用,形成涉及核小体耗尽区域的相互作用中心。调节元件与转录因子、染色质修饰/重塑酶、共激活因子以及介体和/或整合子复合物结合在一起,形成一个转录工厂,类似于液-液相分离的冷凝物。广泛的表观遗传结构域具有支持频繁转录爆发的动态染色质结构。在这篇综述中,我们介绍了广泛的表观遗传领域的当前知识。染色质修饰/重塑酶、共激活因子和介体和/或整合子复合物进入转录工厂,类似于液-液相分离的冷凝物。广泛的表观遗传结构域具有支持频繁转录爆发的动态染色质结构。在这篇综述中,我们介绍了广泛的表观遗传领域的当前知识。染色质修饰/重塑酶、共激活因子和介体和/或整合子复合物进入转录工厂,类似于液-液相分离的冷凝物。广泛的表观遗传结构域具有支持频繁转录爆发的动态染色质结构。在这篇综述中,我们介绍了广泛的表观遗传领域的当前知识。
更新日期:2021-07-08
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