Recruitment of the SWI/SNF chromatin remodeling complex to steroid hormone-regulated promoters by nuclear receptor coactivator flightless-I.
ATP-dependent chromatin remodeling complexes, such as SWI/SNF, are required for transcriptional activation of specific genes and are believed to be recruited to gene promoters by direct interaction with DNA binding transcription factors. However, we report here that recruitment of SWI/SNF to target genes of estrogen receptor alpha (ERalpha) requires the previously described nuclear receptor coactivator protein Flightless-I (Fli-I). Fli-I can bind directly to both ER and BAF53, an actin-related component of the SWI/SNF complex, suggesting that Fli-I may recruit SWI/SNF to ER target genes via interaction with BAF53. Point mutations in Fli-I that disrupt binding to ER or BAF53 compromised the ability of Fli-I to enhance ER-mediated activation of a transiently transfected reporter gene. Depletion of endogenous Fli-I or BAF53 inhibited estrogen-responsive expression of endogenous target genes of ER, indicating a critical role for Fli-I and BAF53. Moreover, depletion of endogenous Fli-I or BAF53 specifically eliminated part of the complex cyclical pattern of recruitment of SWI/SNF to estrogen-responsive promoters in a way that indicates multiple roles and multiple mechanisms of recruitment for SWI/SNF in estrogen-dependent target gene expression. These results begin to establish the functional relationships and interdependencies that coordinate the actions of the many coactivators participating in the transcriptional activation process.
Jeong
Kwang Won
KW
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
Lee
Young-Ho
YH
Stallcup
Michael R
MR
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C116160:ACTL6A protein, human; D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C098179:FLII protein, human; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors