Guest Lecture: Identification of Transcription Factors related to mammalian promoters with distal functions
Jaime Castro-Mondragòn is a PhD student in Bioinformatics. The title of his talk is, 'Identification of Transcription Factors related to mammalian promoters with distal functions'.
Jaime Castro-Mondragòn is a PhD student at the Laboratory of Technical Advances for Genomics and Clinics (TAGC), Aix-Marseille University, Marseille, France.
In humans, the cis-regulatory sequences involved in transcriptional regulation are classified as transcription start site (TSS)-proximal (promoters) and -distal (enhancers). The classical definition states that promoters induce local transcription whilst enhancers do it distally. However, recent studies have found broad similarities among these elements such as chromatin modifications, RNAP recruitment and bidirectional transcription, this would suggest that a portion of promoters could act as bona fide enhancers. Using a high-throughput reporter assay (CapStarr-seq) we measured the potential enhancer activity of ~20,000 human promoters in two cell lines, revealing a small fraction of promoters displaying enhancer activity (E-promoters). Further analysis revealed that these E-promoters were associated with stress response and are enriched in Transcription Factors belonging to the IFN, JUN, YY and STAT families. We found genomic and epigenomic particularities among the E-promoters, and for some of them we demonstrate their function as bona fide enhancers using CRISPR/Cas9 deletion. We suggest that E-promoters might ensure rapid and coordinate regulation of gene expression.