Mapping the cis -regulatory architecture of the human retina reveals noncoding genetic variation in disease
- 7 April 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (16), 9001-9012
- https://doi.org/10.1073/pnas.1922501117
Abstract
The interplay of transcription factors and cis-regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision.Keywords
Funding Information
- HHS | NIH | National Institute of Neurological Disorders and Stroke (R37NS028829)
- HHS | NIH | National Eye Institute (R01 EY028584)
This publication has 74 references indexed in Scilit:
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Transcription factors: from enhancer binding to developmental controlNature Reviews Genetics, 2012
- Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA diseaseNature Neuroscience, 2011
- A unique chromatin signature uncovers early developmental enhancers in humansNature, 2010
- Histone H3K27ac separates active from poised enhancers and predicts developmental stateProceedings of the National Academy of Sciences of the United States of America, 2010
- Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaicVision Research, 2010
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Widespread transcription at neuronal activity-regulated enhancersNature, 2010
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectNature, 2007
- Mutations in CABP4, the Gene Encoding the Ca2+-Binding Protein 4, Cause Autosomal Recessive Night BlindnessAmerican Journal of Human Genetics, 2006