This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/6/1180    most recent 01.ATV.0000163186.58462.c5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huuskonen, J. Articles by Fielding, C. J. Search for Related Content PubMed PubMed Citation Articles by Huuskonen, J. Articles by Fielding, C. J.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1180.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Activation of ATP-Binding Cassette Transporter A1 Transcription by Chromatin Remodeling Complex

Jarkko Huuskonen; Meeta Vishnu; Phoebe E. Fielding; Christopher J. Fielding

From the Cardiovascular Research Institute (J.H., M.V., P.E.F., C.J.F.) and Departments of Medicine (P.E.F) and Physiology (C.J.F.), University of California, San Francisco.

Correspondence to Jarkko Huuskonen, University of California San Francisco, Cardiovascular Research Institute, Box 0130, San Francisco, CA 94143. E-mail jhuu6676{at}itsa.ucsf.edu

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.

Methods and 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.

Catalytic subunits of SWI/SNF chromatin remodeling complex, BRG-1 and brahma, enhanced ABCA1 transcription via the promoter DR-4 element. Physical interaction of LXR/RXR and BRG-1 and recruitment of BRG-1 to ABCA1 promoter was demonstrated. These results indicate that chromatin remodeling regulates ABCA1 transcription.

Key Words: ABCA1 • HDL metabolism • LXR • chromatin remodeling • BRG-1

This article has been cited by other articles:

				M. Chen, W. Li, N. Wang, Y. Zhu, and X. Wang ROS and NF-{kappa}B but not LXR mediate IL-1beta signaling for the downregulation of ATP-binding cassette transporter A1 Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1493 - C1501. [Abstract] [Full Text] [PDF]