AbstractsBiology & Animal Science

Tissue Specific Gene Activation by a Class of Enhancers in Hyperacetylated Domains of Chromatin

by David Rabayev

Institution: University of Rochester
Degree: PhD
Year: 2015
Keywords: Enhancers; Hyperacetylated Domains
Record ID: 2060339
Full text PDF: http://hdl.handle.net/1802/29366


Differential gene expression, both temporal and spatial, is the means by which higher eukaryotic organisms create a variety of tissue and cell types, each performing specialized biological functions. Recent evidence indicates that the primary mechanism by which cell type-specific gene expression is accomplished is via cis-regulation through transcriptional enhancers, which can be located far from sites of transcription initiation. We have previously shown that some gene loci exhibit patterns of covalent histone modifications associated with gene activation at promoters, such as hyperacetylation, extending over large regions (>10 kb), and published studies suggest that these “hyperacetylated domains” are associated with the activity of distal enhancers. We therefore hypothesize that hyperacetylated domains represent a feature of the activity of a specific class of distal enhancer, which in turn functions by a conserved mechanism different from those not associated with such domains. To examine this model more closely, we have examined the murine ferrochelatase (FECH) gene locus in detail, and demonstrate that the region exhibits distinct hyperacetylated domains, associated with distinct, tissue-specific enhancer populations, in both erythroid and hepatic cells. To confirm the activity of these enhancers, we have developed an episomal assay that can distinguish between domain-forming enhancers and enhancers that activate transcription by another mechanism. Our results provide further support for the role of a specific class of transcriptional enhancer in domain formation.