Abstract
Class I histone deacetylases (HDACs) are known to remove acetyl groups from histone tails. This liberates positive charges on the histone tail and allows for tighter winding of DNA, preventing transcription factor binding and gene activation. Although the functions of HDAC proteins are becoming apparent both biochemically and clinically, how this class of proteins is regulated remains poorly understood. We identified a novel interaction between nuclear actin and HDAC 1 and HDAC 2. Nuclear actin has been previously shown to interact with a growing list of nuclear proteins including chromatin remodeling complexes, transcription factors and RNA polymerases. We find that monomeric actin is able to bind the class I HDAC complex. Furthermore, increasing the concentration of actin in HeLa nuclear extracts was able to suppress overall HDAC function. Conversely, polymerizing nuclear actin increased HDAC activity and decreased histone acetylation. Moreover, the interaction between class I HDACs and nuclear actin was found to be activity dependent. Together, our data suggest nuclear actin is able to regulate HDAC 1 and 2 activity.
Highlights
Histone deacetylases (HDACs) are a family of proteins that remove acetyl groups from lysine residues[1,2,3]
Nuclear actin interacts with HDAC 1 and 2
To assess if this was a direct or indirect protein-protein interaction, we covalently coupled purified non-muscle actin, skeletal α-actin, or bovine serum albumin (BSA), as a control, to Sepharose beads. These beads were incubated in HeLa nuclear extract (Fig. 1c) or with purified HDAC 2 (Fig. 1d), precipitated, and probed with HDAC 2 antibody. Both α- and non-muscle actin bound Sepharose brought down more HDAC 2 than BSA Sepharose beads (Fig. 1c) in HeLa nuclear extract, confirming our antibody co-immunoprecipitation experiments (Fig. 1b)
Summary
Histone deacetylases (HDACs) are a family of proteins that remove acetyl groups from lysine residues[1,2,3]. As the acetyl group is removed from lysine residues on histone tails, histones become more basic and are able to tightly wrap around DNA This epigenetic change generally restricts access to transcription machinery and alters nuclear signaling pathways involved in cell proliferation and survival[1,3,4]. HDAC 8 has been shown to interact with skeletal a-actin in the cytoplasm, potentially regulating cell contractility[11]. These studies point to multiple actin-dependent pathways by which HDAC function may be modulated. Together our data suggest nuclear actin is able to bind the active HDAC 1 and 2 complex and attenuate its activity, potentially facilitating chromatin unwinding and gene transcription
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