The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.
The positive transcription elongation factor b is an essential cofactor for the activation of transcription by myocyte enhancer factor 2.
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DOI：
10.1016/j.jmb.2008.07.017
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发表时间：
2008-10-03
影响因子：
5.6
通讯作者：
Fujinaga, Koh
中科院分区：
文献类型：
--
作者：
Nojima, Masanori;Huang, Yehong;Tyagi, Mudit;Kao, Hung-Ying;Fujinaga, Koh
正转录伸长因子b （P-TEFb）由细胞周期蛋白依赖性激酶9和细胞周期蛋白T1组成，通过过度磷酸化RNA聚合酶II的c端区域来刺激转录的伸长。P-TEFb的异常激活导致小鼠心肌肥厚的表现，提示P-TEFb是心肌细胞功能和发育的重要因素。在这里，我们提供的证据表明，P-TEFb选择性地激活由肌细胞增强因子2 （MEF2）转录因子家族介导的转录，MEF2是肌细胞发育的关键调节因子。在小鼠C2C12细胞中，敲低内源性cyclin T1可消除MEF2依赖的报告基因表达以及内源性MEF2靶基因的转录，而P-TEFb的过表达可增强MEF2依赖的转录。P-TEFb在体内和体外都能与MEF2相互作用。血清饥饿诱导MEF2依赖性转录的激活是通过P-TEFb与其抑制亚基HEXIM1的快速解离以及随后P-TEFb募集到MEF2靶基因启动子区域的MEF2结合位点介导的。这些结果表明，P-TEFb的募集是刺激mef2依赖性转录的关键步骤，因此在肌肉细胞的转录程序中提供了一个根本重要的调控机制。
The positive transcription elongation factor b (P-TEFb), composed of cyclin-dependent kinase 9 and cyclin T1, stimulates the elongation of transcription by hyperphosphorylating the C-terminal region of RNA polymerase II. Aberrant activation of P-TEFb results in manifestations of cardiac hypertrophy in mice, suggesting that P-TEFb is an essential factor for cardiac myocyte function and development. Here, we present evidence that P-TEFb selectively activates transcription mediated by the myocyte enhancer factor 2 (MEF2) family of transcription factors, key regulatory factors for myocyte development. Knockdown of endogenous cyclin T1 in murine C2C12 cells abolishes MEF2-dependent reporter gene expression as well as transcription of endogenous MEF2 target genes, whereas overexpression of P-TEFb enhances MEF2-dependent transcription. P-TEFb interacts with MEF2 both in vitro and in vivo. Activation of MEF2-dependent transcription induced by serum starvation is mediated by a rapid dissociation of P-TEFb from its inhibitory subunit, HEXIM1, and a subsequent recruitment of P-TEFb to MEF2 binding sites in the promoter region of MEF2 target genes. These results indicate that recruitment of P-TEFb is a critical step for stimulation of MEF2-dependent transcription, therefore providing a fundamentally important regulatory mechanism underlying the transcriptional program in muscle cells.
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影响因子：
16
作者：
Barboric, M;Nissen, RM;Peterlin, BM
通讯作者：
Peterlin, BM
影响因子：
--
作者：
Iankova, Irena;Petersen, Rasmus K.;Fajas, Lluis
通讯作者：
Fajas, Lluis
影响因子：
5.3
作者：
Hoque, M;Young, TM;Pe'ery, T
通讯作者：
Pe'ery, T
影响因子：
5.4
作者：
Fujinaga, K;Irwin, D;Peterlin, BM
通讯作者：
Peterlin, BM
DOI：
10.1101/sqb.1998.63.371
发表时间：
1998-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Garber, ME;Wei, P;Jones, KA
通讯作者：
Jones, KA