ESR3: Mapping the cis-regulatory landscape of ABCA4 in adult human retina
Partner
Ghent University, Belgium (www.ugent.be/en; www.debaerelab.com) Supervisor Prof. Dr. E. De Baere |
Víctor López Soriano
In 2017, I obtained my bachelor’s degree in Biotechnology at the Miguel Hernandez University (Elche, Spain). During my last year I did an internship under the supervision of Francisco Rodriguez-Valera at the Evolutionary Genomics Group. After that I enrolled to the “Genetics and Evolution” Master’s degree at the University of Granada (Spain) in 2017. I finalized in 2018 with a dissertation tittled “SOX9 function in the maintenance of photoreceptors in transgenic mice” supervised by Doctor F. David Carmona-López. Since May 1st 2019, I joined to Dr. Elfride de Baere’s group in the University of Ghent. My main goal is based on the study of the cis-regulatory elements of the ABCA4 expression. We will study the ABCA4 transcriptional unit, its gene regulatory networks and cis- regulatory landscape of ABCA4 for the first time in human retina. The integration of all functional genomics data generated in this project will lead to fundamental knowledge about the regulation of retinal genes and thus shed light on retinal disease mechanisms. |
Abstract
It is known that ABCA4 is under control of CRX, a key transcription factor (TF) for retinal development and maintenance: a preliminary search for TF binding sites revealed six CRX-binding regions (CBRs) in the ABCA4 region. To add to the cis-regulatory landscape of ABCA4 in human retina, ESR3 will perform ATAC-seq on adult human retinal tissue. To determine that transposase-accessible regions represent active promoters or enhancers, ESR3 will perform ChIP-seq using antibodies specific to H3K27ac and H3K4me2 histone marks and the TF CRX. In addition, ESR3 will perform RNA-seq on adult retina, to enrich for enhancer RNAs (eRNAs), which are bi-directional transcripts that are associated with active enhancers. Finally, ESR1, ESR2 and ESR3 will integrate the cis-regulatory data they generate. ESR3 will assess the effects of selected CREs by ex vivo massively parallel reporter assays in mouse retinas (CRE-seq). With these studies we will generate an integrated functional map of CREs controlling expression in the retina, which are candidate non-coding regions that may be affected in human inherited retinal diseases, such as ABCA4-related IRD.
It is known that ABCA4 is under control of CRX, a key transcription factor (TF) for retinal development and maintenance: a preliminary search for TF binding sites revealed six CRX-binding regions (CBRs) in the ABCA4 region. To add to the cis-regulatory landscape of ABCA4 in human retina, ESR3 will perform ATAC-seq on adult human retinal tissue. To determine that transposase-accessible regions represent active promoters or enhancers, ESR3 will perform ChIP-seq using antibodies specific to H3K27ac and H3K4me2 histone marks and the TF CRX. In addition, ESR3 will perform RNA-seq on adult retina, to enrich for enhancer RNAs (eRNAs), which are bi-directional transcripts that are associated with active enhancers. Finally, ESR1, ESR2 and ESR3 will integrate the cis-regulatory data they generate. ESR3 will assess the effects of selected CREs by ex vivo massively parallel reporter assays in mouse retinas (CRE-seq). With these studies we will generate an integrated functional map of CREs controlling expression in the retina, which are candidate non-coding regions that may be affected in human inherited retinal diseases, such as ABCA4-related IRD.