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SRF 是 KDM2B 和 SET7 在调节骨骼肌分化过程中非组蛋白甲基化的靶点。

SRF is a nonhistone methylation target of KDM2B and SET7 in the regulation of skeletal muscle differentiation.

机构信息

Department of Pharmacology, Chonnam National University Medical School, Hwasun, Republic of Korea.

Vascular Remodeling Research Center, Chonnam National University Medical School, Hwasun, Republic of Korea.

出版信息

Exp Mol Med. 2021 Feb;53(2):250-263. doi: 10.1038/s12276-021-00564-4. Epub 2021 Feb 9.

DOI:10.1038/s12276-021-00564-4
PMID:33564100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8080764/
Abstract

The demethylation of histone lysine residues, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a demethylase of histones H3K4, H3K36, and H3K79 and is associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by the histone methyltransferase SET7. We show that KDM2B inhibited skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and SET7 regulated the balance of SRF K165 methylation. SRF K165 methylation was required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes. SET7 inhibitors blocked muscle cell differentiation. Taken together, these data indicate that SRF is a nonhistone target of KDM2B and that the methylation balance of SRF as maintained by KDM2B and SET7 plays an important role in muscle cell differentiation.

摘要

组蛋白赖氨酸残基的去甲基化是转录调控中最重要的修饰之一，与各种生理状态有关。KDM2B 是组蛋白 H3K4、H3K36 和 H3K79 的去甲基酶，与转录抑制有关。在这里，我们提出了一种新的机制，即 KDM2B 通过去甲基化血清反应因子 (SRF) K165 来负调控肌肉分化，而组蛋白甲基转移酶 SET7 则拮抗这种作用。我们表明，KDM2B 通过抑制 SRF 依赖性基因的转录来抑制骨骼肌分化。KDM2B 和 SET7 都调节了 SRF K165 甲基化的平衡。SRF K165 甲基化对于 SRF 的转录激活和 SRF 依赖性基因的启动子占据是必需的。SET7 抑制剂阻止了肌肉细胞的分化。总之，这些数据表明，SRF 是 KDM2B 的非组蛋白靶标，并且 KDM2B 和 SET7 维持的 SRF 甲基化平衡在肌肉细胞分化中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/ec50d4296376/12276_2021_564_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/2686a2e9bf8d/12276_2021_564_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/d4275e7074b4/12276_2021_564_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/1715c8577dd7/12276_2021_564_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/5014e658227c/12276_2021_564_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/8add66a460dc/12276_2021_564_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/ecc4ca230e6c/12276_2021_564_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/2eb4e99f7c72/12276_2021_564_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/ec50d4296376/12276_2021_564_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/2686a2e9bf8d/12276_2021_564_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/d4275e7074b4/12276_2021_564_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/1715c8577dd7/12276_2021_564_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/5014e658227c/12276_2021_564_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/8add66a460dc/12276_2021_564_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/ecc4ca230e6c/12276_2021_564_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/2eb4e99f7c72/12276_2021_564_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffe/8080764/ec50d4296376/12276_2021_564_Fig8_HTML.jpg

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