Recruitment of the SWI/SNF protein Brg1 by a multiprotein complex effects transcriptional repression in murine erythroid progenitors.
SWI/SNF complexes are involved in both activation and repression of transcription. While one of two homologous ATPases, Brg1 [Brm (Brahma)-related gene 1] or Brm, is required for their chromatin remodelling function, less is known about how these complexes are recruited to DNA. We recently established that a DNA-binding complex containing TAL1/SCL, E47, GATA-1, LMO2 and Ldb1 stimulates P4.2 (protein 4.2) transcription in erythroid progenitors via two E box-GATA elements in the gene's proximal promoter. We show here that the SWI/SNF protein Brg1 is also associated with this complex and that both the E box and GATA DNA-binding sites in these elements are required for Brg1 recruitment. Further, Brg1 occupancy of the P4.2 promoter decreased with terminal erythroid differentiation in association with increased P4.2 transcription, while enforced expression of Brg1 in murine erythroleukaemia cells reduced P4.2 gene expression. Overexpression of Brg1 was associated with increased occupancy of the P4.2 promoter by the nuclear co-repressor mSin3A and HDAC2 (histone deacetylase 2) and with reduced histone H3 and H4 acetylation. Finally, a specific HDAC inhibitor attenuated Brg1-directed repression of P4.2 promoter activity in transfected cells. These results provide insight into the mechanism by which SWI/SNF proteins are recruited to promoters and suggest that transcription of P4.2, and most likely other genes, is actively repressed until the terminal differentiation of erythroid progenitors.
Xu
Zhixiong
Z
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Meng
Xianzhang
X
Cai
Ying
Y
Koury
Mark J
MJ
Brandt
Stephen J
SJ
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D004247:DNA; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; C513194:Smarca4 protein, mouse; D004265:DNA Helicases