Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.
Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.
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DOI：
10.1038/ncomms5322
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发表时间：
2014-07-09
影响因子：
16.6
通讯作者：
Taira M
中科院分区：
文献类型：
--
作者：
Yasuoka Y;Suzuki Y;Takahashi S;Someya H;Sudou N;Haramoto Y;Cho KW;Asashima M;Sugano S;Taira M
由头部选择基因正齿(OTX)决定的头部特征在双边血统中高度保守。然而，OTX和其他转录因子(TF)与基因组相互作用以指导头部形成的分子机制在很大程度上尚不清楚。我们在热带非洲爪哇中使用了CHIP-SEQ和RNA-SEQ方法，发现在早期胚胎阶段，辅阻遏子TLE/Groucho的占据比辅活化子p300更好地指示组织特异性顺式调节模块(CRM)。基于TLE绑定和全面的CRM分析，我们定义了两种不同类型的OTX2和TLE占据的CRM。使用这些装置，OTX2和其他头部组织者TF[例如Lim1/Lhx1(激活子)或Goosecid(抑制子)]能够上调或下调头部组织者中的大量靶基因。一个基本的原理是OTX通过特定类型的CRM标记头部规范的目标基因，由伴侣TF积极或消极地调节。
Head specification by the head-selector gene, orthodenticle (otx) is highly conserved among bilaterian lineages. However, the molecular mechanisms by which Otx and other transcription factors (TFs) interact with the genome to direct head formation, are largely unknown. We employed ChIP-seq and RNA-seq approaches in Xenopus tropicalis gastrulae, and found that occupancy of the corepressor, TLE/Groucho, is a better indicator of tissue-specific cis-regulatory modules (CRMs) than the coactivator p300, during early embryonic stages. Based on TLE binding and comprehensive CRM profiling, we defined two distinct types of Otx2- and TLE-occupied CRMs. Using these devices, Otx2 and other head organizer TFs [e.g., Lim1/Lhx1 (activator) or Goosecoid (repressor)] are able to upregulate or downregulate a large battery of target genes in the head organizer. An underlying principle is that Otx marks target genes for head specification to be regulated positively or negatively by partner TFs through specific types of CRMs.