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Role of Gβγ in regulation of class II histone deacetylases
Author(s) -
Budayeva Hanna,
Hamm Heidi E,
Spiegelberg Bryan D
Publication year - 2010
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.24.1_supplement.457.1
Subject(s) - histone deacetylase 5 , histone deacetylase , transcription factor , histone , biology , g protein coupled receptor , hdac10 , computational biology , acetylation , microbiology and biotechnology , chemistry , dna , genetics , gene , signal transduction
Canonically, G protein‐coupled receptors (GPCRs) participate in biological information flow via their actions at the cell periphery. Recent data, however, have demonstrated the presence of nuclear GPCR‐initiated pathways that have direct access to the genome. We discovered that liberated Gβγ regulates DNA processing through physical interaction with histone deacetylases (HDACs), allowing a fine‐tuning of gene expression upon activation of specific GPCRs. Our work has focused on understanding the mechanisms by which binding to Gβγ inhibits the biological function of class II HDACs. We have found that the interaction occurs, at least in part, within the nucleus. Importantly, we present data that Gβγ interacts directly with the regulatory N‐terminus of HDAC5, which also contains the transcription factor binding domain. We propose a hypothesis that G βγ inhibits HDAC5 by perturbing protein‐protein interactions that are necessary for full functioning of the deacetylase activity. To test this hypothesis, we are developing an in vitro equilibrium binding assay that will allow us to quantitatively characterize Gβγ/HDAC5 complex formation. As proof of concept, we are using this assay to characterize the known interaction between the N‐terminus and the transcription factor MEF2A. We present data characterizing additional interactions of the N‐terminus of HDAC5 with other regulatory proteins.