beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2.

beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2.
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DOI:
10.1016/j.devcel.2010.07.007
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发表时间:
2010-08-17
期刊:
影响因子:
11.8
通讯作者:
Klein, Peter S.
Klein, Peter S.
中科院分区:
生物学1区
文献类型:
--
作者:
Blythe, Shelby A.;Cha, Sang-Wook;Tadjuidje, Emmanuel;Heasman, Janet;Klein, Peter S.

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一个新兴的发展概念是,转录定位以一种反映细胞发育潜力的方式预先设定了基因表达模式。然而,随着发育程序的展开,某些基因座是如何在胚胎中被指定来建立稳定的染色质结构的尚不清楚。我们发现,在非洲爪蟾中胚囊过渡之前的转录静止背景下,Wnt/β-catenin途径的背侧特异性与背侧靶基因表达的开始暂时解耦,β-catenin在目标启动子处建立了平衡的染色质结构。β-catenin招募精氨酸甲基转移酶Prmt2到目标启动子,从而建立不对称二甲基化的H3精氨酸8 (R8)。Prmt2向β-catenin靶基因募集是建立背侧发育程序的必要和充分条件,这表明Prmt2介导的组蛋白H3R8甲基化在β-catenin下游建立稳定的染色质结构和标记关键组织者基因以供后期表达方面起着关键作用。
An emerging concept in development is that transcriptional poising pre-sets patterns of gene expression in a manner that reflects a cell’s developmental potential. However, it is not known how certain loci are specified in the embryo to establish poised chromatin architecture as the developmental program unfolds. We find that, in the context of transcriptional quiescence prior to the midblastula transition in Xenopus, dorsal specification by the Wnt/β-catenin pathway is temporally uncoupled from the onset of dorsal target gene expression, and that β-catenin establishes poised chromatin architecture at target promoters. β-catenin recruits the arginine methyltransferase Prmt2 to target promoters, thereby establishing asymmetrically dimethylated H3 arginine 8 (R8). Recruitment of Prmt2 to β-catenin target genes is necessary and sufficient to establish the dorsal developmental program, indicating that Prmt2-mediated histone H3R8 methylation plays a critical role downstream of β-catenin in establishing poised chromatin architecture and marking key organizer genes for later expression.
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