Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome.
The transcriptional coactivators CBP and P/CAF are required for activation of transcription from the IFN beta enhanceosome. We show that CBP and P/CAF acetylate HMG I(Y), the essential architectural component required for enhanceosome assembly, at distinct lysine residues, causing distinct effects on transcription. Thus, in the context of the enhanceosome, acetylation of HMG I by CBP, but not by P/CAF, leads to enhanceosome destabilization and disassembly. We demonstrate that acetylation of HMG I(Y) by CBP is essential for turning off IFN beta gene expression. Finally, we show that the acetyltransferase activities of CBP and P/CAF modulate both the strength of the transcriptional response and the kinetics of virus-dependent activation of the IFN beta gene.
Munshi
N
N
Department of Biochemistry, and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Merika
M
M
Yie
J
J
Senger
K
K
Chen
G
G
Thanos
D
D
D000107:Acetylation; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019556:COS Cells; D050882:CREB-Binding Protein; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics*; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025741:HMGA1a Protein; D016899:Interferon-beta; D050882:CREB-Binding Protein