NLM DIR Seminar Schedule

Abstract:

Transcription factors (TFs) are DNA-binding proteins that regulate gene expression. TFs occupancies on genome-wide scale are mapped using chromatin immunoprecipitation and sequencing (ChIP-seq) experiments. Numerous analyses of occupancy maps of TFs have reported that the TFs bind to the genomic regions in a highly non-uniform manner. In extreme cases, some regions were observed to be occupied by extremely large numbers of TFs. These regions, called high-occupancy target (HOT) regions, have been reported in human cells as well as in other model organisms. In this study, we used the complete sets of TFs ChIP-seq datasets of the ENCODE Project to analyze these HOT regions. Owing to the sizes of the datasets, we ruled out the possibility of these over-binding phenomena being artifacts. There are both promoter-proximal and gene-distal enhancer HOT regions. They are highly conserved regulatory regions that regulate housekeeping genes and are chromatin accessible across multiple tissues. Furthermore, they are located at the cores of 3D chromatin contact hubs and are associated with disease and loss-of-function mutations. We hypothesize that the existence of an exuberant number of bound TFs in such short genomic regions can be explained by the newly emerging model of large phase-separated transcriptional condensates. This opens an intriguing possibility that the HOT regions might contain information on the regulation of condensates.