Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1.
Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones. Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes. In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601. Complex cII (15 S) contained >/=15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2. The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex. A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers. We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly.
Humphrey
G W
GW
Laboratory of Molecular Growth Regulation, NICHD, National Institutes of Health, Bethesda, Maryland 20892-2753, USA.
Wang
Y
Y
Russanova
V R
VR
Hirai
T
T
Qin
J
J
Nakatani
Y
Y
Howard
B H
BH
D000595:Amino Acid Sequence; D056970:Co-Repressor Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000032:analysis / Q000737:chemistry*; D012256:Riboflavin / Q000032:analysis; D015534:Trans-Activators
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D007527:Isoenzymes; C089320:MTA1 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; C121019:RCOR1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases; D012256:Riboflavin