GENOMIC INTERACTIONS · B-cell development and gene regulation in three dimensions

A major challenge of modern cell biology is to understand how elaborate transcriptional programs drive developmental processes and maintain cellular identity. In mammals temporal and cell type specific gene regulation depend on regulatory elements in the genome. Genome-wide mapping studies have lead to the identification of myriads of regulatory elements. Strikingly these elements not only exist in abundance compared to genes in the genome, but they are also preferentially located distal to transcriptional start sites in intronic or intergenic regions. Therefore, in contrast to promoters, many regulatory elements can be separated by large genomic distances from their target genes and thus their function can not readily be predicted. A growing body of evidence suggests that regulatory elements exert their function through direct physical interactions mediated by chromatin looping. Thus, in order to accurately describe transcriptional networks and gene-regulation in the frame of B-cell development or indeed in any other cell system, these interactions need to be experimentally determined.This proposal aims to map interactions between regulatory elements on a genome-wide scale in early B-cell development. Data will be utilized to generating the first transcriptional networks based on interactions between regulatory elements. Further, transcriptional networks will be integrated with transcriptional profiles to validate accuracy of models. Taken together the proposed project should greatly increase our understanding of how transcriptional networks drive developmental progression within the frame of B-cell differentiation.