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 SET domain of histone methyltransferases MLL3 and MLL4 and HAT domain of histone acetyltransferase p300, respectively, in erythroid K562 cells. The loss of H3K4me1 reduced H3K27ac at the β-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 depletion at putative enhancers was weakened by the loss of H3K4me1 but not by the loss of H3K27ac. Chromatin remodeling complexes were recruited into the β-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 β-globin LCR HSs. These results indicate that H3K4me1 and H3K27ac affect each other in different ways and play more direct roles in nucleosome depletion and eRNA transcription, respectively, at enhancers.

中文翻译：

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组蛋白H3K4me1和H3K27ac在增强子上分别在核小体消耗和eRNA转录中起作用

组蛋白H3K4me1和H3K27ac是增强子特异的修饰，是增强子激活靶基因转录所必需的。然而，这些组蛋白修饰彼此之间的相互影响以及它们在增强子中的作用尚不清楚。在这里，为了比较地分析这些修饰的作用，我们通过删除红系K562细胞中的组蛋白甲基转移酶MLL3的SET结构域和组蛋白乙酰转移酶p300的HAT结构域来抑制H3K4me1和H3K27ac。H3K4me1的丢失使β-珠蛋白增强剂LCR HSs的H3K27ac减少，但H3K27ac的减少并不影响H3K4me1。通过使用ChIP-seq进行全基因组分析，推定的增强子揭示了两个修饰之间的这种不平等关系。H3K4me1的损失减弱了推定增强子上组蛋白H3的消耗，但H3K27ac的损失并未减弱。染色质重塑复合物以H3K4me1依赖性方式募集到β-珠蛋白LCR HS中。相反，增强子RNA（eRNA）转录需要H3K27ac，而H3K4me1不足以实现此目的。强迫H3K27ac诱导eRNA转录，而不影响β-珠蛋白LCR HS的H3K4me1。这些结果表明，H3K4me1和H3K27ac以不同的方式相互影响，并分别在增强子的核小体耗竭和eRNA转录中起更直接的作用。强迫H3K27ac诱导eRNA转录，而不影响β-珠蛋白LCR HS的H3K4me1。这些结果表明，H3K4me1和H3K27ac以不同的方式相互影响，并分别在增强子的核小体耗竭和eRNA转录中起更直接的作用。强迫H3K27ac诱导eRNA转录，而不影响β-珠蛋白LCR HS的H3K4me1。这些结果表明，H3K4me1和H3K27ac以不同的方式相互影响，并分别在增强子处的核小体消耗和eRNA转录中发挥更直接的作用。