Activation of ATP-binding cassette transporter A1 transcription by chromatin remodeling complex.
OBJECTIVE
Liver X receptor (LXR) regulates the transcription of ATP-binding cassette transporter A1 (ABCA1) by binding to the DR-4 promoter element as a heterodimer with retinoid X receptor (RXR). The role of chromatin remodeling complex in LXR or ABCA1 activation has not been established previously. In this study, we investigated the activation of ABCA1 by brahma-related gene 1 (BRG-1) and brahma, members of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin remodeling complex.


RESULTS
Overexpression of wild-type BRG-1 in SW-13 cells, but not a catalytically inactive mutant, increased ABCA1 mRNA levels determined by RT-PCR. These effects were enhanced by LXR and RXR agonists. In 293T (epithelial kidney cell line) and Hep3B (hepatocyte cell line) cells, small interfering RNA against BRG-1/brm also affected ABCA1 mRNA levels. Synergistic activation of ABCA1 was obtained after coexpressing BRG-1 and SRC-1, a coactivator of LXR. Luciferase assays showed that this activation of ABCA1 was dependent on the promoter DR-4 element. Coimmunoprecipitation and chromatin immunoprecipitation studies indicated that the mechanism of BRG-1-mediated activation of ABCA1 involved interaction of LXR/RXR with BRG-1 and binding of this complex to ABCA1 promoter.


CONCLUSIONS
Catalytic subunits of SWI/SNF chromatin remodeling complex, BRG-1 and brahma, play significant roles in enhancing LXR/RXR-mediated transcription of ABCA1 via the promoter DR-4 element.
Huuskonen
Jarkko
J
Cardiovascular Research Institute, University of California San Francisco, CA 94143, USA. jhuu6676@itsa.ucsf.edu
Vishnu
Meeta
M
Fielding
Phoebe E
PE
Fielding
Christopher J
CJ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002460:Cell Line; D002843:Chromatin / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D051548:Histone Acetyltransferases; D006801:Humans; D007668:Kidney / Q000166:cytology; D000071518:Liver X Receptors; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002843:Chromatin; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; C084108:SMARCA4 protein, human; D004265:DNA Helicases