Chromatin is a highly dynamic complex that facilitates the structural transitions required for specific gene expression. An emerging player in the regulation of such chromatin functions are histone H2A variants. These proteins alter the histone-histone and histone-DNA interactions within the nucleosome to generate specialized nucleosomes with dedicated function. In this regard, it is quite possible that the Cterminal tails of H2A proteins confer a direct structural effect by altering the stability or folding potential of nucleosome arrays. This thesis addresses this issue by presenting the biophysical characterization of chromatin particles reconstituted with three different histone H2A variants. H2A.2, an essential protein, destabilizes the nucleosome and reduces the salt-dependent folding propensity of chromatin. H2A-Bbd, a histone variant exclusive to transcriptionally active domains, destabilizes the nucleosome and is more mobile within the nucleus. MacroH2A, which is believed to be involved in transcriptional repression, stabilizes the nucleosome and displays a C-terminal domain that is enriched in a-helix and adopts a globular conformation. Using irnmunochemical analysis it was determined that macroH2A is only found in subphylum vertebrata, is evenly distributed throughout autosomal chromatin at various levels of structure, and has a mutually exclusive relationship with histone HI. Interestingly, the ADP-ribosylation of macroH2A results in a stoichiometric decrease from two copies to one copy of macroH2A in a specific nucleosome, suggesting that the post-translational modification of histone variants may directly regulate nucleosome integrity
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/750 |
| Date | 10 April 2008 |
| Creators | Abbott, D. Wade |
| Contributors | AusioĢ, Juan |
| Source Sets | University of Victoria |
| Detected Language | English |
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