ESR2: Interaction map of cis-regulatory elements controlling ABAC4 in human retina
Abstract
Although the ABCA4 gene was identified over a decade ago, its transcriptional regulation has not been studied in relevant human cells such as retina. Data about CTCF binding sites, DNase I hypersensitivity sites and histone modifications (H3K4me1, H3K27ac) generated in other cell types can be found in publicly available databases (e.g. ENCODE, Roadmap Epigenomics). Here, ESR2 aims to identify and functionally characterise cis-regulatory elements (CREs) controlling ABCA4 expression in adult human retina. ESR2 will first use the recently developed chromosome conformation technique HiChIP to determine the target genes of the CREs that are active in human retinal cells. To that end ESR2 will perform HiChIP using both the Pol II and H3K27ac antibodies that mark active promoters and enhancers, respectively. This will allow us to precisely determine which active enhancers are directly contacting the ABCA4 promoter in human retinal cells. ESR2 will then use stable enhancer transgenic assays in zebrafish to evaluate the spatiotemporal activity of the identified CREs.
Partner
Spanish National Research Council, Seville, Spain (www.csic.es; www.upo.es/CABD/GomezSkarmetaLab)
Supervisor
Prof. Dr. J.L. Gomez-Skarmeta
Although the ABCA4 gene was identified over a decade ago, its transcriptional regulation has not been studied in relevant human cells such as retina. Data about CTCF binding sites, DNase I hypersensitivity sites and histone modifications (H3K4me1, H3K27ac) generated in other cell types can be found in publicly available databases (e.g. ENCODE, Roadmap Epigenomics). Here, ESR2 aims to identify and functionally characterise cis-regulatory elements (CREs) controlling ABCA4 expression in adult human retina. ESR2 will first use the recently developed chromosome conformation technique HiChIP to determine the target genes of the CREs that are active in human retinal cells. To that end ESR2 will perform HiChIP using both the Pol II and H3K27ac antibodies that mark active promoters and enhancers, respectively. This will allow us to precisely determine which active enhancers are directly contacting the ABCA4 promoter in human retinal cells. ESR2 will then use stable enhancer transgenic assays in zebrafish to evaluate the spatiotemporal activity of the identified CREs.
Partner
Spanish National Research Council, Seville, Spain (www.csic.es; www.upo.es/CABD/GomezSkarmetaLab)
Supervisor
Prof. Dr. J.L. Gomez-Skarmeta
