Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mol Cell. 2013 Mar 7;49(5):825-37. doi: 10.1016/j.molcel.2013.01.038.
Emergence of form and function during embryogenesis arises in large part through cell-type- and cell-state-specific variation in gene expression patterns, mediated by specialized cis-regulatory elements called enhancers. Recent large-scale epigenomic mapping revealed unexpected complexity and dynamics of enhancer utilization patterns, with 400,000 putative human enhancers annotated by the ENCODE project alone. These large-scale efforts were largely enabled through the understanding that enhancers share certain stereotypical chromatin features. However, an important question still lingers: what is the functional significance of enhancer chromatin modification? Here we give an overview of enhancer-associated modifications of histones and DNA and discuss enzymatic activities involved in their dynamic deposition and removal. We describe potential downstream effectors of these marks and propose models for exploring functions of chromatin modification in regulating enhancer activity during development.
胚胎发生过程中形态和功能的出现，在很大程度上是通过基因表达模式的细胞类型和细胞状态特异性变化产生的，这种变化是由称为增强子的特殊顺式调控元件介导的。最近的大规模表观基因组图谱揭示了增强子利用模式的出人意料的复杂性和动态性，仅 ENCODE 项目就注释了 40 万个假定的人类增强子。这些大规模的研究在很大程度上是通过了解增强子共享某些典型的染色质特征来实现的。然而，一个重要的问题仍然存在：增强子染色质修饰的功能意义是什么？在这里，我们概述了与增强子相关的组蛋白和 DNA 的修饰，并讨论了参与其动态沉积和去除的酶活性。我们描述了这些标记物的潜在下游效应物，并提出了探索染色质修饰在发育过程中调节增强子活性的功能的模型。
