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Molecular and Cellular Biology, October 2008, p. 5837-5850, Vol. 28, No. 19
0270-7306/08/$08.00+0 doi:10.1128/MCB.00535-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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Division of Molecular Genetics and Biochemistry,1 Division of Cellular and Molecular Biology and Physiology, Department of Biology, Georgia State University, Atlanta, Georgia 303022
Received 2 April 2008/ Returned for modification 20 May 2008/ Accepted 7 July 2008
Recent studies have made evident the fact that the 19S regulatory component of the proteasome has functions that extend beyond degradation, particularly in the regulation of transcription. Although 19S ATPases facilitate chromatin remodeling and acetylation events in yeast (Saccharomyces cerevisiae), it is unclear if they play similar roles in mammalian cells. We have recently shown that the 19S ATPase Sug1 positively regulates the transcription of the critical inflammatory gene for major histocompatibility complex class II (MHC-II) by stabilizing enhanceosome assembly at the proximal promoter. We now show that Sug1 is crucial for regulating histone H3 acetylation at the MHC-II proximal promoter. Sug1 binds to acetylated histone H3 and, in the absence of Sug1, histone H3 acetylation is dramatically decreased at the proximal promoter, with a preferential loss of acetylation at H3 lysine 18. Sug1 also binds to the MHC-II histone acetyltransferase CREB-binding protein (CBP) and is critical for the recruitment of CBP to the MHC-II proximal promoter. Our current study strongly implicates the 19S ATPase Sug1 in modifying histones to initiate MHC-II transcription and provides novel insights into the role of the proteasome in the regulation of mammalian transcription.
Published ahead of print on 28 July 2008.
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