Dr. Bulger is interested in the interplay between tissue-specific gene expression and large-scale patterns of chromatin structure, as well as mechanisms by which enhancers and locus control regions (LCRs) mediate gene activation over large genomic distances. He addresses these questions using genes up-regulated or specifically expressed during late erythroid differentiation, including the b-globin genes, as models. Ongoing or planned projects in his lab include:
(1) Modeling the formation of active chromatin domains in different experimental systems, including stably integrated transgenes in cell culture and reconstituted minichromosomes in cell-free extracts, in order to determine the cis-acting sequences and DNA-binding protein factors involved in their establishment and maintenance;
(2) Characterizing non-genic transcription within the b-globin locus, as well as other loci, and investigating the relationship between such transcription and domain-wide gene regulation;
(3) Identifying factors that facilitate enhancer-promoter and/or LCR-promoter communication at the b-globin locus, in order to gain clues as to how such communication occurs;
(4) Identifying factors that bind to 3'HS1 of the b-globin locus, which is the most prominent site of attachment to nuclear matrix at this region, in order to investigate the relationship between nuclear architecture and gene expression;
(5) Investigating the role of serine protease inhibitors (serpins) in chromatin condensation and gene regulation in differentiating erythroid cells.