KDM4A regulates myogenesis by demethylating H3K9me3 of myogenic regulatory factors.
KDM4A regulates myogenesis by demethylating H3K9me3 of myogenic regulatory factors.
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KDM4A 通过去甲基化生肌调节因子 H3K9me3 来调节肌生成
DOI：
10.1038/s41419-021-03799-1
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发表时间：
2021-05-19
影响因子：
9
通讯作者：
Mo D
中科院分区：
文献类型：
--
作者：
Zhu Q;Liang F;Cai S;Luo X;Duo T;Liang Z;He Z;Chen Y;Mo D
组蛋白赖氨酸脱甲基酶4A（KDM4A）在调节细胞增殖、分化、发育和肿瘤发生中起着重要作用。然而，关于KDM4A在肌肉发育和再生中的功能知之甚少。在这里，我们发现骨骼肌中KDM4A的条件性消融导致胚胎和出生后肌肉形成的损害。卫星细胞中KDM4A的缺失导致肌肉再生缺陷并阻碍卫星细胞的增殖和分化。KDM4A缺陷型成肌细胞的成肌分化和肌管形成受到抑制。染色质免疫沉淀实验表明，KDM4A通过去除MyoD、MyoG和Myf5位点上的组蛋白甲基化标记H3K9me3而促进肌肉发生。此外，KDM4A在成肌细胞中的失活抑制成肌细胞分化并促进H3K9me3水平。在体外敲除KDM4A通过增强细胞周期蛋白依赖性激酶抑制剂P21的表达和降低细胞周期调节剂Cyclin D1的表达来降低成肌细胞增殖。总之，我们的研究结果确定KDM4A作为骨骼肌发育和再生的重要调节因子，协调肌源性细胞增殖和分化。
Histone lysine demethylase 4A (KDM4A) plays a crucial role in regulating cell proliferation, cell differentiation, development and tumorigenesis. However, little is known about the function of KDM4A in muscle development and regeneration. Here, we found that the conditional ablation of KDM4A in skeletal muscle caused impairment of embryonic and postnatal muscle formation. The loss of KDM4A in satellite cells led to defective muscle regeneration and blocked the proliferation and differentiation of satellite cells. Myogenic differentiation and myotube formation in KDM4A-deficient myoblasts were inhibited. Chromatin immunoprecipitation assay revealed that KDM4A promoted myogenesis by removing the histone methylation mark H3K9me3 at MyoD, MyoG and Myf5 locus. Furthermore, inactivation of KDM4A in myoblasts suppressed myoblast differentiation and accelerated H3K9me3 level. Knockdown of KDM4A in vitro reduced myoblast proliferation through enhancing the expression of the cyclin-dependent kinase inhibitor P21 and decreasing the expression of cell cycle regulator Cyclin D1. Together, our findings identify KDM4A as an important regulator for skeletal muscle development and regeneration, orchestrating myogenic cell proliferation and differentiation.
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影响因子：
23.9
作者：
Guenther, Stefan;Kim, Johnny;Kostin, Sawa;Lepper, Christoph;Fan, Chen-Ming;Braun, Thomas
通讯作者：
Braun, Thomas
影响因子：
20.3
作者：
Agger, Karl;Nishimura, Koutarou;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
4.8
作者：
Aziz, Arif;Sebastian, Soji;Dilworth, F. Jeffrey
通讯作者：
Dilworth, F. Jeffrey
DOI：
10.1016/j.bbagrm.2015.07.001
发表时间：
2015-08-01
影响因子：
4.7
作者：
Jung, Eun-Shil;Sim, Ye Ji;Kim, Kye-Seong
通讯作者：
Kim, Kye-Seong
DOI：
10.1242/dev.020966
发表时间：
2009-03
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Nottke A;Colaiácovo MP;Shi Y
通讯作者：
Shi Y