Regulation of acetylation at the major histocompatibility complex class II proximal promoter by the 19S proteasomal ATPase Sug1.
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.
Koues
Olivia I
OI
Division of Molecular Genetics and Biochemistry, Department of Biology, Georgia State University, Atlanta, Georgia 30302, USA.
Dudley
R Kyle
RK
Truax
Agnieszka D
AD
Gerhardt
Dawson
D
Bhat
Kavita P
KP
McNeal
Sam
S
Greer
Susanna F
SF
D000074183:ATPases Associated with Diverse Cellular Activities; D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D008239:Lysine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; D006657:Histones; D060588:LIM Domain Proteins; C092282:PSMC5 protein, human; D014157:Transcription Factors; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; D008239:Lysine