Chk1 Inhibition Hinders the Restoration of H3.1K56 and H3.3K56 Acetylation and Reprograms Gene Transcription After DNA Damage Repair.

Chk1 Inhibition Hinders the Restoration of H3.1K56 and H3.3K56 Acetylation and Reprograms Gene Transcription After DNA Damage Repair.
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DOI:
10.3389/fonc.2022.862592
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发表时间:
2022
影响因子:
4.7
通讯作者:
--
中科院分区:
医学3区
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据报道,H3 K56乙酰化(H3 K56 Ac)在染色质组装中起关键作用;因此,H3 K56 ac参与DNA复制,细胞周期进程,DNA修复和转录激活的调节。为了研究DNA损伤调节剂对组蛋白H3乙酰化和基因转录的影响,表达SNAP标记的H3.1或SNAP标记的H3.3的U2 OS细胞在紫外线(UV)照射后用ATM、ATR或Chk 1抑制剂处理。在不同时间点检查H3.1K56ac、H3.3K56ac和其他H3位点特异性乙酰化的水平,直到UV辐射后24小时。基因转录水平的差异也通过mRNA测序进行了检查。结果表明,Chk 1在H3.1K56ac和H3.3K56ac的恢复中是组蛋白H3 K56乙酰化的重要调节剂。此外,通过化学抑制剂损害Chk 1活性抑制紫外线辐射后的基因转录。这项研究表明,Chk 1在调节H3 K56和其他一些位点特异性H3乙酰化以及在DNA损伤修复过程中重编程基因转录中具有以前未知的作用。
H3K56 acetylation (H3K56Ac) was reported to play a critical role in chromatin assembly; thus, H3K56ac participates in the regulation of DNA replication, cell cycle progression, DNA repair, and transcriptional activation. To investigate the influence of DNA damage regulators on the acetylation of histone H3 and gene transcription, U2OS cells expressing SNAP-labeled H3.1 or SNAP-labeled H3.3 were treated with ATM, ATR, or a Chk1 inhibitor after ultraviolet (UV) radiation. The levels of H3.1K56ac, H3.3K56ac, and other H3 site-specific acetylation were checked at different time points until 24 h after UV radiation. The difference in gene transcription levels was also examined by mRNA sequencing. The results identified Chk1 as an important regulator of histone H3K56 acetylation in the restoration of both H3.1K56ac and H3.3K56ac. Moreover, compromising Chk1 activity via chemical inhibitors suppresses gene transcription after UV radiation. The study suggests a previously unknown role of Chk1 in regulating H3K56 and some other site-specific H3 acetylation and in reprograming gene transcription during DNA damage repair.
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