Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4
Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4
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DOI：
10.1101/gad.201327.112
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发表时间：
2012-12-01
影响因子：
10.5
通讯作者：
Shilatifard, Ali
中科院分区：
文献类型：
--
作者：
Herz, Hans-Martin;Mohan, Man;Shilatifard, Ali
组蛋白H3在Lys 4上的单甲基化（H3 K4 me 1）和组蛋白H3在Lys 27上的乙酰化（H3 K27 ac）是在活跃转录的基因体和增强子上高度富集的组蛋白修饰。虽然在酵母中所有的H3 K4甲基化模式，包括H3 K4 me 1，都是由Set 1/COMPASS（与Set 1相关的蛋白质复合物）实现的，但在果蝇中有三类COMPASS样复合物可以在增强子上实现H3 K4 me 1：dSet 1，Trithorax和Trithorax相关（Trr）。在这里，我们报告，Trr，果蝇同源的哺乳动物Mll 3/4 COMPASS样复合物，可以作为一个主要的H3 K4单甲基转移酶的增强子在体内发挥作用。Trr的缺失导致各种组织中H3 K4 me 1和H3 K27 ac水平的整体降低。用切翅边缘增强子的测定暗示Trr在增强子介导的过程中的功能作用。全基因组分析表明，Trr是维持H3 K4 me 1和H3 K27 ac染色质特征所必需的，这类似于增强子所描述的组蛋白修饰模式。此外，在哺乳动物系统中的研究表明，在类似的过程中的Trr同系物Mll 3的作用。由于Trr和哺乳动物Mll 3/4复合物的区别在于具有独特的亚基，H3 K27脱甲基酶UTX，我们提出了一个模型，其中H3 K4单甲基转移酶Trr/Mll 3/Mll 4和H3 K27脱甲基酶UTX合作，以调节从非活性/平衡到活性增强子的过渡。
Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.