Open AccessCell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors andcis-regulatory modules in the retina
Author(s) -
Charles Chan,
Nicolas Lonfat,
Rong Zhao,
A. Edward Davis,
Liang Li,
Man Wu,
Cheng Hui Lin,
Zhe Ji,
Constance L. Cepko,
Sui Wang
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.187922
Subject(s) - biology , transcription factor , retina , microbiology and biotechnology , transcription (linguistics) , cell , cell type , genetics , gene , neuroscience , linguistics , philosophy
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 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 utilize a cohort of TFs with different expression patterns, and multiple CRMs with different chromatin configurations, to precisely regulate the expression of Otx2.