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组蛋白单甲基化控制染色质和转录中的 PARP-1。

Mono-methylated histones control PARP-1 in chromatin and transcription.

机构信息

Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, United States.

Fox Chase Cancer Center, Philadelphia, United States.

出版信息

Elife. 2024 May 1;13:RP91482. doi: 10.7554/eLife.91482.

DOI:10.7554/eLife.91482
PMID:38690995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11062633/
Abstract

PARP-1 is central to transcriptional regulation under both normal and stress conditions, with the governing mechanisms yet to be fully understood. Our biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. We found that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of PARP-1-dependent loci during both development and heat shock stress. Here, we report that the sole H4K20 mono-methylase, , and mutants undergo developmental arrest. RNA-seq analysis showed an absolute correlation between PR-SET7- and PARP-1-dependent loci expression, confirming co-regulation during developmental phases. PARP-1 and PR-SET7 are both essential for activating and other heat shock genes during heat stress, with a notable increase of H4K20me1 at their gene body. Mutating disrupts monomethylation of H4K20 along heat shock loci and abolish PARP-1 binding there. These data strongly suggest that H4 monomethylation is a key triggering point in PARP-1 dependent processes in chromatin.

摘要

PARP-1 在正常和应激条件下的转录调控中起着核心作用，但调控机制尚未完全理解。我们的生化和基于 ChIP-seq 的分析表明，PARP-1 特异性结合于活性组蛋白标记，特别是 H4K20me1。我们发现 H4K20me1 在促进 PARP-1 结合和调节发育和热休克应激过程中的 PARP-1 依赖基因座方面起着关键作用。在这里，我们报告说唯一的 H4K20 单甲基转移酶 和 突变体经历发育停滞。RNA-seq 分析显示 PR-SET7 和 PARP-1 依赖基因座表达之间存在绝对相关性，这证实了发育阶段的共调控。PARP-1 和 PR-SET7 在热应激期间激活 和其他热休克基因都是必不可少的，其基因体上 H4K20me1 的含量显著增加。突变 破坏了热休克基因座上 H4K20 的单甲基化，并在此处消除了 PARP-1 的结合。这些数据强烈表明，H4 单甲基化是染色质中 PARP-1 依赖过程的关键触发点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/b21874363a36/elife-91482-fig5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/c4c2bfb6a404/elife-91482-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/06d8a291384b/elife-91482-fig3-figsupp4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/601e6c469638/elife-91482-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/b21874363a36/elife-91482-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/0cd090e82fc2/elife-91482-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/387479993b21/elife-91482-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/8d12140a3f90/elife-91482-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/6b3d2ecf84df/elife-91482-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/a262520240c4/elife-91482-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/8697a49c73a0/elife-91482-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/cefa7ad3a6d1/elife-91482-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/c4c2bfb6a404/elife-91482-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/06d8a291384b/elife-91482-fig3-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/204cfd9c9b16/elife-91482-fig3-figsupp5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/601e6c469638/elife-91482-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed3/11062633/b21874363a36/elife-91482-fig5.jpg

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H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning in .
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