Abstract
Hda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 Å. The ARB2 domain displays an α/β sandwich architecture with an arm protruding outside. Two ARB2 domain molecules form a compact homo-dimer via the arm elements, and assemble as an inverse “V” shape. The pull-down and ITC results reveal that the ARB2 domain possesses the histone binding ability, recognizing both the H2A-H2B dimer and H3-H4 tetramer. Perturbation of the dimer interface abolishes the histone binding ability of the ARB2 domain, indicating that the unique dimer architecture of the ARB2 domain coincides with the function for anchoring to histone. Collectively, our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda1 HDAC complex.
Highlights
Hda[1] is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events
The size-exclusion chromatography assay shows that the mutant ARB2-M0 eluted with a molecular weight of approximately 29 kDa, which is coincident with the theoretical value of a monomer. These results strongly suggest that the ARB2 domain of Hda[1] exists as a homodimer, and this is consistent with the fact that the Hda[1] protein functions as a dimer during the deacetylation reaction[17]
The yeast class II Hda[1] HDAC complex shows similarity to the mammalian class II HDACs, such as HDAC4, HDAC5, HDAC6, HDAC7, HDAC9 and HDAC10, which play an essential role in nucleosomal repression of transcription
Summary
Hda[1] is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda[1] HDAC complex. The structural unit of chromatin is the nucleosome that contains 147 bp of DNA wrapping around an octamer composed of two molecules each of the four histones-H2A, H2B, H3, and H4. The tails of these histones are unstructured and protruding from the core component[1]. Until now, there are still no structural and functional indications for the ARB2 domain
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