Nodal signaling recruits the histone demethylase Jmjd3 to counteract polycomb-mediated repression at target genes.
Nodal signaling recruits the histone demethylase Jmjd3 to counteract polycomb-mediated repression at target genes.
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DOI：
10.1126/scisignal.2000841
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发表时间：
2010-06-22
影响因子：
7.3
通讯作者：
Kuehn MR
中科院分区：
文献类型：
--
作者：
Dahle Ø;Kumar A;Kuehn MR
细胞间信号传导和表观遗传机制都调节胚胎发育，但尚不清楚它们如何整合以建立和维持谱系特异性基因表达程序。在这里，我们表明，一个关键的功能的发展必需的Nodal-Smads 2/3（Smad 2和Smad 3）信号通路是招募组蛋白去甲基化酶Jmjd 3的目标基因，从而抵消抑制Polycomb。Smads 2/3与Jmjd 3结合，并以依赖于活性Nodal信号传导的方式将其募集到染色质中。单独敲低Jmjd 3显著降低Nodal靶基因表达，而在不存在Polycomb的情况下，靶基因座独立于Nodal信号传导表达。这些数据确立了Polycomb在靶基因表达中对Nodal信号传导的依赖性，并揭示了发育信号传导如何与表观遗传过程整合以控制基因表达。
Both intercellular signaling and epigenetic mechanisms regulate embryonic development, but it is unclear how they are integrated to establish and maintain lineage-specific gene expression programs. Here, we show that a key function of the developmentally essential Nodal-Smads2/3 (Smad2 and Smad3) signaling pathway is to recruit the histone demethylase Jmjd3 to target genes, thereby counteracting repression by Polycomb. Smads2/3 bound to Jmjd3 and recruited it to chromatin in a manner that was dependent on active Nodal signaling. Knockdown of Jmjd3 alone substantially reduced Nodal target gene expression, whereas in the absence of Polycomb, target loci were expressed independently of Nodal signaling. These data establish a role for Polycomb in imposing a dependency on Nodal signaling for the expression of target genes and reveal how developmental signaling integrates with epigenetic processes to control gene expression.
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影响因子：
4.6
作者：
Dunn, NR;Vincent, SD;Bikoff, EK
通讯作者：
Bikoff, EK
影响因子：
10.5
作者：
Barradas, Marta;Anderton, Emma;Gil, Jesus
通讯作者：
Gil, Jesus
影响因子：
10.5
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
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