Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and cis-regulatory modules in the retina
Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and cis-regulatory modules in the retina
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DOI：
10.1242/dev.187922
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Wang, Sui
中科院分区：
文献类型：
--
作者：
Chan, Candace S. Y.;Lonfat, Nicolas;Wang, Sui
转录因子（TF）通常在发育和稳态过程中重复使用，以控制相同和/或不同细胞环境中的不同过程。考虑到基因组中TF的数量有限以及需要调控的事件数量巨大，TF的再利用是必要的。我们分析了如何表达的同源异型框TF，orthodentide同源异型框2（Otx 2），在小鼠视网膜发育过程中的细胞类型和阶段特异性的方式进行调节。我们确定了7个OW顺式调节模块（CRM），其中05，07和09 CRM标志着三个不同的细胞环境的Otx 2表达。我们发现，Otx 2，Crx和Sox 2，这是众所周知的TF调节视网膜发育，结合并激活O 5，O 7或O 9 CRM，分别。这三个标准物质的染色质状态被发现是不同的在体内不同的视网膜细胞类型和在不同的阶段。我们的结论是，视网膜细胞使用一组具有不同表达模式的TF和具有不同染色质构型的多个CRM来精确地调节Otx 2的表达。
Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodentide homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven OW cis-regulatory modules (CRMs), among which the 05, 07 and 09 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in vivo in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.