University of California, Irvine, Department of Biological Sciences, Molecular Biology and Biochemistry

Dr. Barbara A. Hamkalo

(Ph.D., University of Massachusetts, 1968)

Molecular basis of differential chromatin condensation

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    Publications via PubMed (NIH National Library of Medicine)

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  • Molecular analysis of centromeric heterochromatin; function of an yeast H1-like protein

    My laboratory studies the molecular and cell biological organization of vertebrate centromeric heterochromatin. Current studies are directed towards the identification of proteins preferentially associated with centromeres which may be involved in differential chromatin condensation (a hallmark of heterochromatin) and regulation of gene expression. Previous work focused on isoforms of histone H1, known to be involved in chromatin condensation. Subtype-specific antibodies were used to show that inactive sequences and heterochromatin possess all isoforms whereas active genes are selectively depleted of certain subtypes, possibly increasing access to regulatory factors and the transcriptional machinery. Centromeric satellite DNA has been purified as chromatin in order to identify novel centromeric proteins. At least a dozen nonhistones are enriched in the purified material and are the subject of continued research. The existence of expressed "heterochromatin" genes in vertebrates is also under investigation since gene expression is typically associated with decondensation so that genes embedded in heterochromatin are likely to be regulated by unique mechanisms. Finally, we are investigating the function of a yeast gene product which possesses structural hallmarks of H1 but which is non-essential. Using genetics and molecular and cell biological approaches we hope to shed light on the functional evolution of this conserved chromosomal protein.

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