Department of Pathology, University of Michigan, Ann Arbor, United States of America.
Department of Biological Chemistry, University of Michigan, Ann Arbor, United States of America.
Biochim Biophys Acta Gene Regul Mech. 2020 Jul;1863(7):194561. doi: 10.1016/j.bbagrm.2020.194561. Epub 2020 Apr 15.
In eukaryotes, histone H3K4 methylation by the MLL/SET1 family histone methyltransferases is enriched at transcription regulatory elements including gene promoters and enhancers. The level of H3K4 methylation is highly correlated with transcription activation and is one of the most frequently used histone post-translational modifications to predict transcriptional outcome. Recently, it has been shown that rearrangement of the cellular landscape of H3K4 mono-methylation at distal enhancers precedes cell fate transition and is used for identification of novel regulatory elements for development and disease progression. Similarly, broad H3K4 tri-methylation regions have also been used to predict intrinsic tumor suppression properties of regulator regions in a variety of cellular models. Understanding the regulation for how H3K4 methylation is deposited and regulated is of paramount importance. In this review, we will discuss new findings on how the MLL/SET1 family enzymes are regulated on chromatin and their potential functional and regulatory implications. This article is part of a Special Issue entitled: The MLL family of proteins in normal development and disease edited by Thomas A Milne.
在真核生物中，MLL/SET1 家族组蛋白甲基转移酶催化的组蛋白 H3K4 甲基化富集于转录调控元件，包括基因启动子和增强子。H3K4 甲基化的水平与转录激活高度相关，是预测转录结果的最常用的组蛋白翻译后修饰之一。最近，已经表明，远端增强子处 H3K4 单甲基化的细胞景观重排先于细胞命运转变，并用于鉴定发育和疾病进展的新调控元件。同样，广泛的 H3K4 三甲基化区域也被用于预测多种细胞模型中调控区的内在肿瘤抑制特性。了解 H3K4 甲基化如何沉积和调控的机制至关重要。在这篇综述中，我们将讨论关于 MLL/SET1 家族酶在染色质上如何被调控及其潜在的功能和调控意义的新发现。本文是由 Thomas A Milne 编辑的题为“正常发育和疾病中的 MLL 家族蛋白”的特刊的一部分。
