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Biochemical and Biophysical Characterization of Histone Deacetylase Recruitment to the Sin3L/Rpd3L Corepressor Complex
Author(s) -
Marcum Ryan,
Radhakrishnan Ishwar
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.877.18
Subject(s) - corepressor , histone , acetylation , histone deacetylase , context (archaeology) , chromatin , microbiology and biotechnology , hdac11 , biology , chemistry , computational biology , biochemistry , gene expression , gene , repressor , paleontology
Histone modifications play an important role in modulating chromatin dynamics with concomitant effects on gene expression. Acetylation of histone lysine residues is regulated by the opposing actions of histone acetylases (HATs) and deacetylases (HDACs). These enzymes are commonly found in large, multi‐protein complexes and changes in expression or activity of HDACs are associated with multiple diseased states including certain cancers. Despite considerable interest in HDACs as therapeutic targets, there is a significant gap in our knowledge about the structure and mechanism of action of these enzymes in the context of their respective complexes. We describe our attempts to reconstitute and structurally characterize the key subunits of the HDAC‐associated Sin3L/Rpd3L corepressor complex in order to clarify the precise molecular role(s) of the core subunits. Our biochemical and biophysical characterizations suggest that nuclear HDACs 1 and 2 are recruited to the Sin3L/Rpd3L complex through multivalent interactions with multiple core components of the Sin3L/Rpd3L complex and that small molecules have a role in regulating efficient HDAC recruitment to the complex. This work was supported by grants from the National Institute of Health (NIH GM64715)and the American Heart Association (AHA 14GRNT20170003).