Interrogating Histone Acetylation and BRD4 as Mitotic Bookmarks of Transcription
Interrogating Histone Acetylation and BRD4 as Mitotic Bookmarks of Transcription
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DOI：
10.1016/j.celrep.2019.03.057
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发表时间：
2019-04-09
期刊：
影响因子：
8.8
通讯作者：
Blobel, Gerd A.
中科院分区：
文献类型：
--
作者：
Behera, Vivek;Stonestrom, Aaron J.;Blobel, Gerd A.
染色质组织的整体变化和有丝分裂期间转录的停止被认为是有丝分裂后适当转录模式的恢复的挑战。乙酰赖氨酸结合蛋白BRD4以前被认为是有丝分裂染色质上的转录“书签”。在这里，BRD4在红系细胞中的全基因组位置分析，结合数据归一化和峰表征方法，揭示了BRD4广泛占据有丝分裂染色质。然而，从有丝分裂染色质中去除BRD4不会损害有丝分裂后转录的激活。此外，组蛋白质谱揭示了在有丝分裂过程中大多数翻译后修饰（PTM）的全局保存。特别地，H3K14ac、H3K27ac、H3K122ac和H4K16ac广泛地标记有丝分裂染色质，特别是在谱系特异性基因处，并且预测BRD4有丝分裂结合基因组范围。因此，BRD4可能不是有丝分裂的书签，而只是一个“乘客”。相反，有丝分裂组蛋白乙酰化模式可能构成了有丝分裂后恢复谱系特异性转录模式的实际书签。
Global changes in chromatin organization and the cessation of transcription during mitosis are thought to challenge the resumption of appropriate transcription patterns after mitosis. The acetyl-lysine binding protein BRD4 has been previously suggested to function as a transcriptional "bookmark" on mitotic chromatin. Here, genome-wide location analysis of BRD4 in erythroid cells, combined with data normalization and peak characterization approaches, reveals that BRD4 widely occupies mitotic chromatin. However, removal of BRD4 from mitotic chromatin does not impair post-mitotic activation of transcription. Additionally, histone mass spectrometry reveals global preservation of most posttranslational modifications (PTMs) during mitosis. In particular, H3K14ac, H3K27ac, H3K122ac, and H4K16ac widely mark mitotic chromatin, especially at lineage-specific genes, and predict BRD4 mitotic binding genome wide. Therefore, BRD4 is likely not a mitotic bookmark but only a "passenger." Instead, mitotic histone acetylation patterns may constitute the actual bookmarks that restore lineage-specific transcription patterns after mitosis.