Journal article
A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors
Cell reports (Cambridge), Vol.17(5), pp.1247-1254
10/25/2016
DOI: 10.1016/j.celrep.2016.09.066
PMCID: PMC5123866
PMID: 27783940
Abstract
Transcription factors often activate and repress different target genes in the same cell. How activation and repression are encoded by different arrangements of transcription factor binding sites in cis-regulatory elements is poorly understood. We investigated how sites for the transcription factor CRX encode both activation and repression in photo-receptors by assaying thousands of genomic and synthetic cis-regulatory elements in wild-type and Crx(-/-) retinas. We found that sequences with high affinity for CRX repress transcription, whereas sequences with lower affinity activate. This rule is modified by a cooperative interaction between CRX sites and sites for the transcription factor NRL, which overrides the repressive effect of high affinity for CRX. Our results show how simple rearrangements of transcription factor binding sites encode qualitatively different responses to a single transcription factor and explain how CRX plays multiple cis-regulatory roles in the same cell.
Details
- Title: Subtitle
- A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors
- Creators
- Michael A. White - Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63110 USAJamie C. Kwasnieski - Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63110 USAConnie A. Myers - Washington University in St. LouisSusan Q. Shen - Washington University in St. LouisJoseph C. Corbo - Washington University in St. LouisBarak A. Cohen - Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63110 USA
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.17(5), pp.1247-1254
- DOI
- 10.1016/j.celrep.2016.09.066
- PMID
- 27783940
- PMCID
- PMC5123866
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- R01GM092910 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) HG006346; GM092910 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HG006790 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
- Language
- English
- Date published
- 10/25/2016
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984618512802771
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