title: Acetylation of histone deacetylase 1 regulates NuRD corepressor complex activity.
abstract: BACKGROUND
  HDAC1-containing NuRD complex is required for GATA-1-mediated repression and activation.
  
  
  RESULTS
  GATA-1 associated with acetylated HDAC1-containing NuRD complex, which has no deacetylase activity, for gene activation.
  
  
  CONCLUSIONS
  Acetylated HDAC1 converts NuRD complex from a repressor to an activator during GATA-1-directed erythroid differentiation program.
  
  
  CONCLUSIONS
  HDAC1 acetylation may function as a master regulator for the activity of HDAC1 containing complexes. Histone deacetylases (HDACs) play important roles in regulating cell proliferation and differentiation. The HDAC1-containing NuRD complex is generally considered as a corepressor complex and is required for GATA-1-mediated repression. However, recent studies also show that the NuRD complex is involved in GATA-1-mediated gene activation. We tested whether the GATA-1-associated NuRD complex loses its deacetylase activity and commits the GATA-1 complex to become an activator during erythropoiesis. We found that GATA-1-associated deacetylase activity gradually decreased upon induction of erythroid differentiation. GATA-1-associated HDAC1 is increasingly acetylated after differentiation. It has been demonstrated earlier that acetylated HDAC1 has no deacetylase activity. Indeed, overexpression of an HDAC1 mutant, which mimics acetylated HDAC1, promotes GATA-1-mediated transcription and erythroid differentiation. Furthermore, during erythroid differentiation, acetylated HDAC1 recruitment is increased at GATA-1-activated genes, whereas it is significantly decreased at GATA-1-repressed genes. Interestingly, deacetylase activity is not required for Mi2 remodeling activity, suggesting that remodeling activity may be required for both activation and repression. Thus, our data suggest that NuRD can function as a coactivator or repressor and that acetylated HDAC1 converts the NuRD complex from a repressor to an activator during GATA-1-directed erythroid differentiation.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Jian
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.forename: Constance
authors.initials: C
authors.lastname: Noguchi
authors.forename: Jörg
authors.initials: J
authors.lastname: Bungert
authors.forename: Suming
authors.initials: S
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
chemical_list: D056970:Co-Repressor Proteins; D050982:GATA1 Transcription Factor; D056284:Histone Deacetylase 1; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex