Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
复制标题
DOI：
10.1093/nar/gku813
复制
发表时间：
2014-10
影响因子：
14.9
通讯作者：
McDermott JC
中科院分区：
文献类型：
--
作者：
Wales S;Hashemi S;Blais A;McDermott JC
MEF2 在心肌和骨骼肌谱系的转录调节中发挥着深远的作用。为了定义重叠且独特的 MEF2A 基因组靶标，我们利用心肌细胞和骨骼肌母细胞的 ChIP-exo 分析。在骨骼肌成肌细胞和心肌细胞中分别有 2783 个和 1648 个 MEF2A 结合峰中，鉴定出 294 个共同结合位点。将基因组目标与 MEF2A 耗尽的肌原细胞的 RNA-seq 分析中的差异表达基因进行比较，揭示了两个显着的遗传网络。与肌肉发育主要相关的基因因 MEF2A 的缺失而下调，而上调的基因则揭示了 MEF2A 在抑制生长/增殖基因方面以前未被识别的功能。选择几个上调（Tprg、Mctp2、Kitl、Prrx1、Dusp6）和下调（Atp1a2、Hspb7、Tmem182、Sorbs2、Lmod3）MEF2A 靶基因进行进一步研究。有趣的是，针对 MEF2A/D 异二聚体的 siRNA 揭示了 Dusp6（一种 MAPK 磷酸酶）在心脏和骨骼肌源性谱系中的调节作用有些不同。此外，MEF2D 在成肌细胞中充当 Dusp6 的 p38MAPK 依赖性阻遏物。这些数据表明 MEF2 在骨骼肌和心肌谱系中协调信号依赖性基因表达的常见和非重叠程序。
MEF2 plays a profound role in the regulation of transcription in cardiac and skeletal muscle lineages. To define the overlapping and unique MEF2A genomic targets, we utilized ChIP-exo analysis of cardiomyocytes and skeletal myoblasts. Of the 2783 and 1648 MEF2A binding peaks in skeletal myoblasts and cardiomyocytes, respectively, 294 common binding sites were identified. Genomic targets were compared to differentially expressed genes in RNA-seq analysis of MEF2A depleted myogenic cells, revealing two prominent genetic networks. Genes largely associated with muscle development were down-regulated by loss of MEF2A while up-regulated genes reveal a previously unrecognized function of MEF2A in suppressing growth/proliferative genes. Several up-regulated (Tprg, Mctp2, Kitl, Prrx1, Dusp6) and down-regulated (Atp1a2, Hspb7, Tmem182, Sorbs2, Lmod3) MEF2A target genes were chosen for further investigation. Interestingly, siRNA targeting of the MEF2A/D heterodimer revealed a somewhat divergent role in the regulation of Dusp6, a MAPK phosphatase, in cardiac and skeletal myogenic lineages. Furthermore, MEF2D functions as a p38MAPK-dependent repressor of Dusp6 in myoblasts. These data illustrate that MEF2 orchestrates both common and non-overlapping programs of signal-dependent gene expression in skeletal and cardiac muscle lineages.
登录
查看更多内容
DUSP6/MKP-3对FGF信号传导的负反馈调节由ERK1/2驱动，并由ETS因子与DUSP6/MKP-3基因启动子内的保守位点结合介导。
DOI：
10.1042/bj20071512
发表时间：
2008-06-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Ekerot M;Stavridis MP;Delavaine L;Mitchell MP;Staples C;Owens DM;Keenan ID;Dickinson RJ;Storey KG;Keyse SM
通讯作者：
Keyse SM
影响因子：
10.5
作者：
LI, L;CHAMBARD, JC;OLSON, EN
通讯作者：
OLSON, EN
影响因子：
4.9
作者：
Dionyssiou MG;Salma J;Bevzyuk M;Wales S;Zakharyan L;McDermott JC
通讯作者：
McDermott JC
影响因子：
20.1
作者：
Auger-Messier M;Accornero F;Goonasekera SA;Bueno OF;Lorenz JN;van Berlo JH;Willette RN;Molkentin JD
通讯作者：
Molkentin JD
影响因子：
56.9
作者：
Lin, Q;Schwarz, J;Olson, EN
通讯作者：
Olson, EN