Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells.

Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells.
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DOI:
10.1371/journal.pone.0092689
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Aoki F
Aoki F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yukawa M;Akiyama T;Franke V;Mise N;Isagawa T;Suzuki Y;Suzuki MG;Vlahovicek K;Abe K;Aburatani H;Aoki F

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通过染色质免疫沉淀测序,在小鼠胚胎干细胞中同时研究了大多数H2A和H3变体(H2A、H2AX、H2AZ、macroH2A、H3.1、H3.2和H3.3)的全基因组分布。在转录起始位点周围,组蛋白变体分布在具有高CpG密度和低CpG密度启动子的基因之间不同,无论其表达水平如何。在基因间区域,调控元件在H2A.Z和H3.3中富集,而重复元件分别在H2A和macroH2A和H3.1中丰富。组成核小体的H2A和H3变体组合的分析揭示,H2A.Z和H3.3组合在整个基因组中以比其他组合更高的频率存在,表明H2A.Z和H3.3优先彼此缔合以独立于基因组区域地组成核小体。最后,我们发现染色质仅在H2A.Z和H3.3都富集的区域不稳定,但在仅H3.3丰富的区域强烈定量稳定。因此,组蛋白变体组成是染色质结构的重要决定因素,而染色质结构与特定的基因组功能相关。
Genome-wide distribution of the majority of H2A and H3 variants (H2A, H2AX, H2AZ, macroH2A, H3.1, H3.2 and H3.3) was simultaneously investigated in mouse embryonic stem cells by chromatin immunoprecipitation sequencing. Around the transcription start site, histone variant distribution differed between genes possessing promoters of high and low CpG density, regardless of their expression levels. In the intergenic regions, regulatory elements were enriched in H2A.Z and H3.3, whereas repeat elements were abundant in H2A and macroH2A, and H3.1, respectively. Analysis of H2A and H3 variant combinations composing nucleosomes revealed that the H2A.Z and H3.3 combinations were present at a higher frequency throughout the genome than the other combinations, suggesting that H2A.Z and H3.3 associate preferentially with each other to comprise the nucleosomes independently of genome region. Finally, we found that chromatin was unstable only in regions where it was enriched in both H2A.Z and H3.3, but strongly quantified stable in regions in which only H3.3 was abundant. Therefore, histone variant composition is an important determinant of chromatin structure, which is associated with specific genomic functions.
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