Linking Maintenance of Chromosome Structure to Transcriptional Regulation

Whitehead Institute For Biomedical Res, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The precise regulation of gene expression in the cell is an important task only accomplished by the coordination of multiple molecular pathways. One of these pathways involves the regulation of transcription by chromosome structural components. Aberrant control of chromosome structure is associated with a variety of developmental syndromes, deformities, and the progression of tumors due to the misregulation of genes. Recent evidence has linked chromosome structure to gene expression via the formation of DNA loops that bring enhancers in proximity to promoters during enhancer-loop-mediated transcription. Stem cells represent an ideal cell type to dissect transcriptional regulation due to their unique abilities to differentiate into any cell type of an organism, and alo self-renew. To study the molecular processes regulating transcription of the genome we will employ high-throughput genomic-based technologies and methodologies. The objective of this proposed research is to understand the role of Condensin, a protein complex required for the structural maintenance of chromosomes, in mediating transcription. We will map the distribution of Condensin on the genome and we will identify factors responsible for recruitment and distribution of Condensin. We will examine the pattern of genome-wide occupancy of Condensin with other known members of the transcriptional apparatus and also correlate this pattern with gene expression data. Uncovering the function of chromosome structure in transcription remains a largely unexplored area of research and should be considered essential in fully appreciating the interplay between the various processes that influence gene expression programs in the cell.