KAP1-associated transcriptional inhibitory complex regulates C2C12 myoblasts differentiation and mitochondrial biogenesis via miR-133a repression
KAP1-associated transcriptional inhibitory complex regulates C2C12 myoblasts differentiation and mitochondrial biogenesis via miR-133a repression
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KAP1 相关转录抑制复合物通过 miR-133a 抑制调节 C2C12 成肌细胞分化和线粒体生物发生
DOI：
10.1038/s41419-020-02937-5
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发表时间：
2020-09
影响因子：
9
通讯作者：
Taotao Wei
中科院分区：
文献类型：
--
作者：
Jialing Zhang;Chaoju Hua;Yu Zhang;Peng Wei;Yaping Tu;Taotao Wei
成肌细胞的分化对于生物个体的生长和肌肉组织的重建起着关键作用。一些 microRNA 在成肌细胞分化过程中显着上调，并且它们的靶基因已被探索。然而，microRNA 转录调控的分子机制仍然难以捉摸。在本研究中，我们发现miR-133a的表达在C2C12成肌细胞的分化过程中增加。 miR-133a 模拟物足以诱导线粒体的生物发生和 C2C12 成肌细胞的分化，而 miR-133a 抑制剂则消除细胞分化。利用CRISPR原位亲和纯化调控元件（CAPTURE）技术，我们进一步剖析了miR-133a表达的调控机制，发现KAP1相关转录复合物导致了C2C12成肌细胞中miR-133a的抑制。 KAP1 的敲除增加了 miR-133a 的表达，这有助于线粒体的生物发生和 C2C12 成肌细胞的分化。据我们所知，这是首次利用CAPTURE技术鉴定miR-133a在细胞分化过程中的调控因子的研究，这可能为理解microRNA在不同生物过程中的精准调控机制提供新思路。
The differentiation of myoblasts plays a key role in the growth of biological individuals and the reconstruction of muscle tissue. Several microRNAs are significantly upregulated during the differentiation of myoblasts and their target genes have been explored. However, the molecular mechanisms underlying the transcriptional regulation of microRNAs remain elusive. In the present study, we found that the expression of miR-133a is increased during the differentiation of C2C12 myoblasts. miR-133a mimic is sufficient to induce the biogenesis of mitochondria and differentiation of C2C12 myoblasts whereas miR-133a inhibitor abolishes cell differentiation. Using CRISPR affinity purification in situ of regulatory elements (CAPTURE) technique, we further dissected the regulatory mechanisms of miR-133a expression and found that KAP1-associated transcription complex accounts for the suppression of miR-133a in C2C12 myoblasts. Knockdown of KAP1 increased the expression of miR-133a, which contributed to the biogenesis of mitochondria and differentiation of C2C12 myoblasts. To our knowledge, this is the first study using the CAPTURE technology to identify the regulatory factors of miR-133a during cell differentiation, which may provide new ideas for understanding the precision regulatory machinery of microRNAs during different biological processes.
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影响因子：
--
作者：
Wagatsuma A;Sakuma K
通讯作者：
Sakuma K
影响因子：
64.5
作者：
Zhang X;Zuo X;Yang B;Li Z;Xue Y;Zhou Y;Huang J;Zhao X;Zhou J;Yan Y;Zhang H;Guo P;Sun H;Guo L;Zhang Y;Fu XD
通讯作者：
Fu XD
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
通过生物素化 dCas9 原位捕获染色质相互作用
影响因子：
64.5
作者：
Liu X;Zhang Y;Chen Y;Li M;Zhou F;Li K;Cao H;Ni M;Liu Y;Gu Z;Dickerson KE;Xie S;Hon GC;Xuan Z;Zhang MQ;Shao Z;Xu J
通讯作者：
Xu J
影响因子：
3.7
作者：
Shen L;Chen L;Zhang S;Du J;Bai L;Zhang Y;Jiang Y;Li X;Wang J;Zhu L
通讯作者：
Zhu L