Open AccessEnhancer transcription identifies cis-regulatory elements for photoreceptor cell types
Author(s) -
Carlos Perez-Cervantes,
Linsin A Smith,
Rangarajan D. Nadadur,
Andrew Hughes,
Sui Wang,
Joseph C. Corbo,
Constance L. Cepko,
Nicolas Lonfat,
Ivan P. Moskowitz
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.184432
Subject(s) - biology , non coding rna , enhancer , transcription factor , rna , cell type , computational biology , epigenetics , context (archaeology) , genetics , microbiology and biotechnology , gene , cell , paleontology
Identification of cell-type specific cis-regulatory elements (CREs) is critical for understanding development and disease, although identification of functional regulatory elements remains challenging. We hypothesized that context-specific CREs could be identified by context-specific non-coding RNA (ncRNA) profiling, based on the observation that active CREs produce ncRNAs. We applied ncRNA profiling to identify rod and cone photoreceptor CREs from wild-type and mutant mouse retinas, defined by presence or absence of the rod-specific transcription factor (TF), Nrl, respectively. Nrl-dependent ncRNA expression strongly correlated with epigenetic profiles of rod and cone photoreceptors, identified thousands of candidate rod- and cone-specific CREs, and identified motifs for rod- and cone-specific TFs. Colocalization of NRL and the retinal TF CRX correlated with rod-specific ncRNA expression, whereas CRX alone favored cone-specific ncRNA expression, providing quantitative evidence that heterotypic TF interactions distinguish cell type-specific CRE activity. We validated the activity of novel Nrl-dependent ncRNA-defined CREs in developing cones. This work supports differential ncRNA profiling as a platform for the identification of cell-type specific CREs and discovery of molecular mechanisms underlying TF-dependent CRE activity.