Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers
Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers
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DOI：
10.1096/fj.202100488r
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发表时间：
2021-08-01
期刊：
影响因子：
4.8
通讯作者：
Kim, AeRi
中科院分区：
文献类型：
--
作者：
Kang, Yujin;Kim, Yea Woon;Kim, AeRi
组蛋白H3K4me1和H3K27ac是增强子特异性修饰，是增强子激活靶基因转录所必需的。然而，这些组蛋白修饰的相互作用及其在增强子中的作用尚不清楚。为了比较分析这些修饰的作用，我们在红系K562细胞中分别通过删除组蛋白甲基转移酶MLL3和MLL4的SET结构域以及组蛋白乙酰转移酶p300的HAT结构域来抑制H3K4me1和H3K27ac。H3K4me1的缺失降低了β -珠蛋白增强子LCR HSs上的H3K27ac，但H3K27ac的缺失对H3K4me1没有影响。通过使用ChIP-seq进行全基因组分析，在假定的增强子中揭示了两种修饰之间的不平等关系。H3K4me1的缺失减弱了组蛋白H3在假定增强子上的释放，而H3K27ac的缺失则没有。染色质重塑复合物以h3k4me1依赖的方式被招募到β -珠蛋白LCR HSs中。相比之下，H3K27ac是增强子RNA （eRNA）转录所必需的，而H3K4me1是不够的。强迫h3k27ac诱导eRNA转录而不影响β -珠蛋白LCR HSs的H3K4me1。这些结果表明H3K4me1和H3K27ac以不同的方式相互影响，分别在增强子核小体排出和eRNA转录中发挥更直接的作用。
Histone H3K4me1 and H3K27ac are enhancer-specific modifications and are required for enhancers to activate transcription of target genes. However, the reciprocal effects of these histone modifications on each other and their roles in enhancers are not clear. Here to comparatively analyze the role of these modifications, we inhibited H3K4me1 and H3K27ac by deleting the SET domains of histone methyltransferases MLL3 and MLL4 and the HAT domain of histone acetyltransferase p300, respectively, in erythroid K562 cells. The loss of H3K4me1 reduced H3K27ac at the beta-globin enhancer LCR HSs, but H3K27ac reduction did not affect H3K4me1. This unequal relationship between two modifications was revealed in putative enhancers by genome-wide analysis using ChIP-seq. Histone H3 eviction at putative enhancers was weakened by the loss of H3K4me1 but not by the loss of H3K27ac. Chromatin remodeling complexes were recruited into the beta-globin LCR HSs in a H3K4me1-dependent manner. In contrast, H3K27ac was required for enhancer RNA (eRNA) transcription, and H3K4me1 was not enough for it. Forced H3K27ac-induced eRNA transcription without affecting H3K4me1 at the beta-globin LCR HSs. These results indicate that H3K4me1 and H3K27ac affect each other in different ways and play more direct roles in nucleosome eviction and eRNA transcription, respectively, at enhancers.