Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-beta promoter.

Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. In this report, we show that virus infection of cells results in a dramatic hyperacetylation of histones H3 and H4 that is localized to the IFN-beta promoter. Furthermore, expressing a truncated version of IRF-3, which lacks a p300/CBP interaction domain, suppresses both histone hyperacetylation and activation of the IFN-beta gene. Thus, coactivator-mediated localized hyperacetylation of histones may play a crucial role in inducible gene expression.

[1]  G. Huez,et al.  Regulation of gene expression by cytokines and virus in human cells lacking the type-I interferon locus. , 1992, European journal of biochemistry.

[2]  C. Allis,et al.  Steroid receptor coactivator-1 is a histone acetyltransferase , 1997, Nature.

[3]  N. Jones,et al.  p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells. , 1998, Genes & development.

[4]  T. Taniguchi,et al.  Involvement of the IRF family transcription factor IRF‐3 in virus‐induced activation of the IFN‐β gene , 1998, FEBS letters.

[5]  J. Hiscott,et al.  Virus-Dependent Phosphorylation of the IRF-3 Transcription Factor Regulates Nuclear Translocation, Transactivation Potential, and Proteasome-Mediated Degradation , 1998, Molecular and Cellular Biology.

[6]  T. Maniatis,et al.  The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome. , 1997, Molecular cell.

[7]  C. D. Allis,et al.  Linking histone acetylation to transcriptional regulation , 1998, Cellular and Molecular Life Sciences CMLS.

[8]  M. Grunstein,et al.  Spreading of transcriptional represser SIR3 from telomeric heterochromatin , 1996, Nature.

[9]  M. Merika,et al.  Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. , 1998, Molecular cell.

[10]  C. Allis,et al.  Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation , 1996, Cell.

[11]  R. Evans,et al.  Nuclear Receptor Coactivator ACTR Is a Novel Histone Acetyltransferase and Forms a Multimeric Activation Complex with P/CAF and CBP/p300 , 1997, Cell.

[12]  Andrew J. Bannister,et al.  The CBP co-activator is a histone acetyltransferase , 1996, Nature.

[13]  P. Moore,et al.  Regulation of Type I Interferon Gene Expression by Interferon Regulatory Factor-3* , 1998, The Journal of Biological Chemistry.

[14]  Tae Hoon Kim,et al.  Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Claudio Nicolini,et al.  Chromatin Structure and Function , 1979, NATO Advanced Study Institutes Series.

[16]  M. Carey,et al.  The Enhanceosome and Transcriptional Synergy , 1998, Cell.

[17]  N. Reich,et al.  Interferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1 , 1998, Molecular and Cellular Biology.

[18]  E. Nishida,et al.  Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF‐3 and CBP/p300 , 1998, The EMBO journal.

[19]  M. Gerritsen,et al.  CREB-binding protein/p300 are transcriptional coactivators of p65. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Vettese-Dadey,et al.  Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. , 1996, The EMBO journal.

[21]  T. Maniatis,et al.  Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. , 1998, Molecular cell.

[22]  A. Wolffe,et al.  Acetylation of general transcription factors by histone acetyltransferases , 1997, Current Biology.

[23]  K. Nightingale,et al.  Histone acetylation facilitates RNA polymerase II transcription of the Drosophila hsp26 gene in chromatin , 1998, The EMBO journal.

[24]  R. Eckhardt,et al.  Chromatin and Chromosome Structure , 1977 .

[25]  K. Struhl,et al.  Targeted Recruitment of the Sin3-Rpd3 Histone Deacetylase Complex Generates a Highly Localized Domain of Repressed Chromatin In Vivo , 1998, Molecular and Cellular Biology.

[26]  J. V. Falvo,et al.  Structure and Function of the Interferon-β Enhanceosome , 1998 .

[27]  J. Hiscott,et al.  Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[28]  C. Allis,et al.  Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines , 1996, Nature.

[29]  J. Davie,et al.  Covalent modifications of histones: expression from chromatin templates. , 1998, Current opinion in genetics & development.

[30]  M. Grunstein.  Histone acetylation in chromatin structure and transcription , 1997, Nature.

[31]  S. Schreiber,et al.  Nuclear histone acetylases and deacetylases and transcriptional regulation: HATs off to HDACs. , 1997, Current opinion in chemical biology.

[32]  J. Parvin,et al.  Factors associated with the mammalian RNA polymerase II holoenzyme. , 1998, Nucleic acids research.

[33]  T. Maniatis,et al.  Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome , 1995, Cell.

[34]  Alan P. Wolffe,et al.  A positive role for histone acetylation in transcription factor access to nucleosomal DNA , 1993, Cell.

[35]  K. Struhl.  Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[36]  Wei Gu,et al.  Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain , 1997, Cell.

[37]  A. Wolffe,et al.  Histone acetylation: chromatin in action. , 1997, Trends in biochemical sciences.

[38]  G. Schroth,et al.  Studies of the DNA binding properties of histone H4 amino terminus. Thermal denaturation studies reveal that acetylation markedly reduces the binding constant of the H4 "tail" to DNA. , 1993, The Journal of biological chemistry.

[39]  W. Zhang,et al.  Acetylation and modulation of erythroid Krüppel-like factor (EKLF) activity by interaction with histone acetyltransferases. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Grant,et al.  Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  B. Turner.  Decoding the nucleosome , 1993, Cell.

[42]  M. David,et al.  Cytomegalovirus Activates Interferon Immediate-Early Response Gene Expression and an Interferon Regulatory Factor 3-Containing Interferon-Stimulated Response Element-Binding Complex , 1998, Molecular and Cellular Biology.

[43]  Andrew J. Bannister,et al.  The TAFII250 Subunit of TFIID Has Histone Acetyltransferase Activity , 1996, Cell.

[44]  Jeffrey D. Parvin,et al.  RNA Helicase A Mediates Association of CBP with RNA Polymerase II , 1997, Cell.

[45]  R. Paro,et al.  Analysis of chromatin structure by in vivo formaldehyde cross-linking. , 1997, Methods.

[46]  M. Grunstein,et al.  Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3 , 1998, Nature.

[47]  B. Howard,et al.  A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A , 1996, Nature.

[48]  T. R. Hebbes,et al.  A direct link between core histone acetylation and transcriptionally active chromatin. , 1988, The EMBO journal.

[49]  C. Allis,et al.  Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. , 1998, Genes & development.

[50]  B. Howard,et al.  The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases , 1996, Cell.

[51]  M. Pazin,et al.  What's Up and Down with Histone Deacetylation and Transcription? , 1997, Cell.