Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA 94304, USA.
Departments of Genetics and Ophthalmology, Blavatnik Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Development. 2020 Jul 26;147(14):dev187922. doi: 10.1242/dev.187922.
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 -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 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.
转录因子（TFs）在发育和内稳态过程中经常被重复使用，以控制同一和/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，而需要调节的事件数量巨大，TF 的重复使用是必要的。我们分析了同源盒 TF orthodenticle homeobox 2 (Otx2) 的表达如何在小鼠视网膜发育过程中以细胞类型和阶段特异性的方式被调控。我们鉴定了七个 -调控模块（CRMs），其中 O5、O7 和 O9 CRMs 标志着 Otx2 表达的三个不同的细胞环境。我们发现，Otx2、Crx 和 Sox2 是众所周知的调节视网膜发育的 TF，分别结合并激活 O5、O7 或 O9 CRMs。这三个 CRM 的染色质状态在不同的视网膜细胞类型和不同的阶段是不同的。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 和多个具有不同染色质构型的 CRM，来精确调控 Otx2 的表达。
