Premium
Chromatin dynamics, DNA‐binding transcription factors and lens differentiation
Author(s) -
Cvekl Ales
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8018
Subject(s) - chromatin , enhancer , biology , transcription factor , chia pet , regulation of gene expression , cellular differentiation , gene , microbiology and biotechnology , genetics , gene regulatory network , pax6 , regulatory sequence , gene expression , computational biology , chromatin remodeling
Purpose Lens differentiation is an advantageous model to study how chromatin structure and dynamics (“open” and “closed” chromatin) regulates gene expression of both regulatory factors and proteins needed for intricate lens fiber cell structure and function. Our purpose was to map and explain dynamic changes in local chromatin structure of genes during lens differentiation at genome‐wide level. Methods ATAC‐seq experiments were conducted using epithelia and fibers from E14.5 and newborn (P0.5) mouse lenses. RNA‐seq data from similar samples were included in the analysis. Results Open chromatin changes were defined through identification of differentially accessible regions coupled with differential gene expression during lens differentiation. Lens‐specific regulatory regions are shown using ES cells, forebrain, and liver. Two pathways were identified: epiE14.5 → fibE14.5 → fibP0.5 (path1) and epiE14.5 → epiP0.5 (path2). Unbiased cis ‐motif analysis of “open” regions corresponding to promoters and enhancers revealed the cis ‐regulatory principles of lens differentiation via known (e.g. AP‐1, Ets, Hsf4, Maf, and Pax6) and novel (e.g. CTCF, Tead, and NF1) motifs. Conclusions The current data support a general model of dynamic changes in open chromatin associated with transcriptional activities of functionally related genes that required for lens fiber cell differentiation and epithelial maturation. Together, the data pave the road for detailed studies of lens‐specific enhancers, identification of gene regulatory networks underlying lens morphogenesis, and identification of cataract‐causing mutation in non‐coding regulatory sequences.