Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.
Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.
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DOI：
10.1016/j.devcel.2017.02.017
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发表时间：
2017-03-27
影响因子：
11.8
通讯作者：
Cho KW
中科院分区：
文献类型：
--
作者：
Charney RM;Forouzmand E;Cho JS;Cheung J;Paraiso KD;Yasuoka Y;Takahashi S;Taira M;Blitz IL;Xie X;Cho KW
转录因子和染色质之间的相互作用决定了基因调控网络的活性。胚层特化与合子基因激活紧密相关，在大多数后生动物中，取决于母体因素。我们探讨了Foxh 1（一种介导Nodal/TGFβ信号传导的母体转录因子）在中内胚层特化过程中顺式调节模块（CRM）的动态全基因组相互作用。Foxh 1在卵裂阶段标记CRMs，并在早期囊胚中招募辅助阻遏物Tle/Groucho。我们强调了一个人口的标准物质，不断占据Foxh 1，并显示他们是由H3 K4 me 1，Ep 300，和福克斯/袜/Smad图案标记，这表明这些因素之间的相互作用在基因调控。我们还建议在这些标准物质中，母体Foxh 1和合子Foxa之间存在分子“交接”，以维持增强子的激活。我们的研究结果表明，Foxh 1的功能在一个层次的相互作用，标记发育基因的激活开始与合子基因表达的发病。母体转录因子如何控制早期胚胎中基因调控网络的启动尚不清楚。Charney等人证明了在合子基因激活之前母体Foxh 1与胚胎基因组的动态结合。他们阐明了时间招聘的辅助因子顺式调控模块控制中内胚层规范。
The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGFβ signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1, and show they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular ‘hand-off’ between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation beginning with the onset of zygotic gene expression. How maternal transcription factors control the onset of gene regulatory networks in the early embryo is poorly understood. Charney et al. demonstrate dynamic binding of maternal Foxh1 to the embryonic genome well before zygotic gene activation. They elucidate the temporal recruitment of co-factors to cis-regulatory modules controlling mesendoderm specification.