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Abstract：
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, orthodenticle homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven Otx2 cis-regulatory modules (CRMs), among which the O5, O7 and O9 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.
摘要：
转录因子(TF)通常在发育和稳态期间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TFs数量有限，需要调节的事件数量巨大，重复使用TFs是必要的。我们分析了homeoboxTF的表达，正统同源盒2(Otx2)，在小鼠视网膜发育过程中以细胞类型和阶段特异性方式调节。我们确定了七个Otx2顺式调节模块(CRM)，其中O5，O7和O9CRM标记了Otx2表达的三种不同的细胞背景。我们发现Otx2，Crx和Sox2是众所周知的调节视网膜发育的TFs，绑定并激活O5、O7或O9CRM，分别。发现这三种CRM的染色质状态在不同的视网膜细胞类型和不同的阶段在体内是不同的。我们得出结论，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来精确调节Otx2的表达。
