Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products

Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products
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肌细胞生成素独立于其他肌肉特异性基因产物诱导肌细胞特异性增强子结合因子 MEF-2

DOI:
10.1128/mcb.11.10.4854-4862.1991
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发表时间:
1991
影响因子:
5.3
通讯作者:
Eric N. Olson
Eric N. Olson
中科院分区:
生物学2区
文献类型:
--
作者:
Peter Cserjesi;Eric N. Olson

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肌细胞特异性增强子结合因子MEF-2是一种核因子,与肌肉肌酸激酶和肌球蛋白轻链1/3增强子中的保守元件相互作用。A. Gossett,D. J. Kelvin,E. A.斯滕贝格和E. N.奥尔森,摩尔。Cell. 9:5022-5033,1989)。我们在这项研究中表明,MEF-2是由生肌调节因子myogenin和有丝分裂信号阻断这种调节相互作用。肌细胞生成素对MEF-2的诱导发生在已被肌细胞生成素转化为成肌细胞的转染的10 T1/2细胞中,以及在不响应肌细胞生成素激活肌细胞生成程序的CV-1肾细胞中。通过MEF-2位点的诱变,我们进一步确定了MEF-2的结合位点要求,并在许多肌肉特异性调控区中鉴定了潜在的MEF-2位点。还发现MEF-2位点结合一种普遍存在的核因子,其结合特异性与MEF-2相似但不同。我们的研究结果表明,MEF-2的控制,无论是直接或间接的,由肌细胞生成素依赖性的调节途径,并建议生长因子信号抑制MEF-2的表达,通过抑制肌细胞生成素的表达或活性。肌细胞生成素在CV-1细胞中诱导MEF-2活性的能力(其不激活与终末分化相关的下游基因)也表明肌细胞生成素在不允许肌细胞生成的细胞类型中保留有限的功能,并表明MEF-2独立于其他肌肉特异性基因进行调节。
The myocyte-specific enhancer-binding factor MEF-2 is a nuclear factor that interacts with a conserved element in the muscle creatine kinase and myosin light-chain 1/3 enhancers (L. A. Gossett, D. J. Kelvin, E. A. Sternberg, and E. N. Olson, Mol. Cell. Biol. 9:5022-5033, 1989). We show in this study that MEF-2 is regulated by the myogenic regulatory factor myogenin and that mitogenic signals block this regulatory interaction. Induction of MEF-2 by myogenin occurs in transfected 10T1/2 cells that have been converted to myoblasts by myogenin, as well as in CV-1 kidney cells that do not activate the myogenic program in response to myogenin. Through mutagenesis of the MEF-2 site, we further defined the binding site requirements for MEF-2 and identified potential MEF-2 sites within numerous muscle-specific regulatory regions. The MEF-2 site was also found to bind a ubiquitous nuclear factor whose binding specificity was similar to but distinct from that of MEF-2. Our results reveal that MEF-2 is controlled, either directly or indirectly, by a myogenin-dependent regulatory pathway and suggest that growth factor signals suppress MEF-2 expression through repression of myogenin expression or activity. The ability of myogenin to induce MEF-2 activity in CV-1 cells, which do not activate downstream genes associated with terminal differentiation, also demonstrates that myogenin retains limited function within cell types that are nonpermissive for myogenesis and suggests that MEF-2 is regulated independently of other muscle-specific genes.
人类肌肉肌酸激酶基因的发育调节和组织特异性表达。
DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
作者:
Trask,RV;Strauss,AW;Billadello,JJ
通讯作者: Billadello,JJ
DOI: 10.1073/pnas.88.4.1242
发表时间: 1991-02
影响因子: 11.1
作者:
B. Wentworth;M. Donoghue;J. Engert;E. B. Berglund;N. Rosenthal
通讯作者: B. Wentworth;M. Donoghue;J. Engert;E. B. Berglund;N. Rosenthal
DOI: 10.1101/gad.2.12b.1779
发表时间: 1988-12-01
影响因子: 10.5
作者:
DONOGHUE, M;ERNST, H;ROSENTHAL, N
通讯作者: ROSENTHAL, N
DOI: 10.1126/science.2814500
发表时间: 1989-11-10
期刊: SCIENCE
影响因子: 56.9
作者:
MUELLER, PR;WOLD, B
通讯作者: WOLD, B
DOI: 10.1128/mcb.9.11.5022
发表时间: 1989-11-01
影响因子: 5.3
作者:
GOSSETT, LA;KELVIN, DJ;OLSON, EN
通讯作者: OLSON, EN