Assembly of a Functional Beta Interferon Enhanceosome Is Dependent on ATF-2–c-jun Heterodimer Orientation

ABSTRACT Heterodimeric transcription factors, including the basic region-leucine zipper (bZIP) protein ATF-2–c-jun, are well-characterized components of an enhanceosome that mediates virus induction of the human beta interferon (IFN-β) gene. Here we report that within the IFN-β enhanceosome the ATF-2–c-jun heterodimer binds in a specific orientation, which is required for assembly of a complex between ATF-2–c-jun and interferon regulatory factor 3 (IRF-3). We demonstrate that correct orientation of the ATF-2–c-jun binding site is required for virus induction of the IFN-β gene and for IRF-3-dependent activation of a composite ATF-2– c-jun–IRF site in the IFN-β promoter. We also show that in vitro the DNA-bound ATF-2–c-jun heterodimer adopts a fixed orientation upon the binding of IRF-3 at an adjacent site in the IFN-β enhancer and that the DNA-binding domain of IRF-3 is sufficient to mediate this effect. In addition, we show that the DNA-binding domain of ATF-2 is necessary and sufficient for selective protein-protein interactions with IRF-3. Strikingly, in vivo chromatin immunoprecipitation experiments with IFN-β reporter constructs reveal that recruitment of IRF-3 to the IFN-β promoter upon virus infection is dependent on the orientation of the ATF-2–c-jun heterodimer binding site. These observations demonstrate functional and physical cooperativity between the bZIP and IRF transcription factor families and illustrate the critical role of heterodimeric transcription factors in formation of the IFN-β enhanceosome.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  T. Taniguchi,et al.  Crystal structure of an IRF‐DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences , 1999, The EMBO journal.

[3]  M. Merika,et al.  The role of HMG I(Y) in the assembly and function of the IFN‐β enhanceosome , 1999, The EMBO journal.

[4]  K. Georgopoulos,et al.  Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes , 1999, The EMBO journal.

[5]  J. Hiscott,et al.  Structural and Functional Analysis of Interferon Regulatory Factor 3: Localization of the Transactivation and Autoinhibitory Domains , 1999, Molecular and Cellular Biology.

[6]  R. Maki,et al.  Mutation analysis of the Pip interaction domain reveals critical residues for protein-protein interactions. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Brass,et al.  Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers , 1999, The EMBO journal.

[8]  G. Verdine,et al.  The orientation of the AP-1 heterodimer on DNA strongly affects transcriptional potency. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[9]  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.

[10]  T. Kerppola,et al.  DNA bending determines Fos–Jun heterodimer orientation , 1998, Nature Structural Biology.

[11]  T. Kerppola,et al.  Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1-Fos-Jun-ARRE2 complex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  T. Mak,et al.  Cooperative interaction between the DNA-binding domains of PU.1 and IRF4. , 1998, Journal of molecular biology.

[13]  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.

[14]  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.

[15]  S. Harrison,et al.  Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA , 1998, Nature.

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

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

[18]  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.

[19]  D. Dean,et al.  Rb Interacts with Histone Deacetylase to Repress Transcription , 1998, Cell.

[20]  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.

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

[22]  G. Ghosh,et al.  Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA , 1998, Nature.

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

[24]  A. Aggarwal,et al.  Structure of IRF-1 with bound DNA reveals determinants of interferon regulation , 1998, Nature.

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

[26]  M. Merika,et al.  Intra- and intermolecular cooperative binding of high-mobility-group protein I(Y) to the beta-interferon promoter , 1997, Molecular and cellular biology.

[27]  E. Zandi,et al.  AP-1 function and regulation. , 1997, Current opinion in cell biology.

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

[29]  T. Collins,et al.  Tumor Necrosis Factor α-Induced E-selectin Expression Is Activated by the Nuclear Factor-κB and c-JUN N-terminal Kinase/p38 Mitogen-activated Protein Kinase Pathways* , 1997, The Journal of Biological Chemistry.

[30]  G. Orphanides,et al.  High-resolution mapping of nucleoprotein complexes by site-specific protein-DNA photocrosslinking: organization of the human TBP-TFIIA-TFIIB-DNA quaternary complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  E. Rothenberg,et al.  A dynamic assembly of diverse transcription factors integrates activation and cell-type information for interleukin 2 gene regulation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Rao,et al.  Tumor necrosis factor alpha gene regulation in activated T cells involves ATF-2/Jun and NFATp , 1996, Molecular and cellular biology.

[33]  Dimitris Thanos,et al.  Reversal of intrinsic DNA bends in the IFNβ gene enhancer by transcription factors and the architectural protein HMG I(Y) , 1995, Cell.

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

[35]  T. Richmond,et al.  Crystal structure of a bZIP/DNA complex at 2.2 A: determinants of DNA specific recognition. , 1995, Journal of molecular biology.

[36]  J. Glover,et al.  Only one of the two DNA-bound orientations of AP-1 found in solution cooperates with NFATp , 1995, Current Biology.

[37]  P. Verde,et al.  Heterodimerization of c-Jun with ATF-2 and c-Fos is required for positive and negative regulation of the human urokinase enhancer. , 1995, Oncogene.

[38]  P. Sigler,et al.  Structural determinants of nuclear receptor assembly on DNA direct repeats , 1995, Nature.

[39]  C. Carlberg,et al.  Natural vitamin D3 response elements formed by inverted palindromes: polarity-directed ligand sensitivity of vitamin D3 receptor-retinoid X receptor heterodimer-mediated transactivation , 1995, Molecular and cellular biology.

[40]  T. Maniatis,et al.  Identification of the rel family members required for virus induction of the human beta interferon gene , 1995, Molecular and cellular biology.

[41]  H. Nash,et al.  Specific photocrosslinking of DNA-protein complexes: identification of contacts between integration host factor and its target DNA. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[42]  G. Nabel,et al.  An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation , 1994, Molecular and cellular biology.

[43]  A. Deisseroth,et al.  Interaction of nuclear proteins with an AP‐1/CRE‐like promoter sequence in the human TNF‐α gene , 1994 .

[44]  Michael R. Green,et al.  Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains , 1994, Nature.

[45]  M. Green,et al.  HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. , 1993, Science.

[46]  T. Maniatis,et al.  Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements , 1993, Cell.

[47]  G. Nabel,et al.  A cooperative interaction between NF‐kappa B and Sp1 is required for HIV‐1 enhancer activation. , 1993, The EMBO journal.

[48]  P. Herrlich,et al.  Heterodimer formation of cJun and ATF‐2 is responsible for induction of c‐jun by the 243 amino acid adenovirus E1A protein. , 1993, The EMBO journal.

[49]  Dimitris Thanos,et al.  The High Mobility Group protein HMG I(Y) is required for NF-κB-dependent virus induction of the human IFN-β gene , 1992, Cell.

[50]  T. Maniatis,et al.  An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected]. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[51]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[52]  P. Baeuerle,et al.  NF‐kappa B contacts DNA by a heterodimer of the p50 and p65 subunit. , 1991, The EMBO journal.

[53]  A. Siddiqui,et al.  HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions , 1991, Science.

[54]  Tsonwin Hai,et al.  Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[55]  T. Taniguchi,et al.  Absence of the type I IFN system in EC cells: Transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated , 1990, Cell.

[56]  K. Yamamoto,et al.  Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. , 1990, Science.

[57]  S. Tapscott,et al.  Id: A Negative Regulator of Helix‐Loop‐Helix DNA Binding Proteins , 1990, Annals of the New York Academy of Sciences.

[58]  I. Verma,et al.  Association of nuclear oncoproteins fos and jun. , 1989, Current opinion in cell biology.

[59]  Michael R. Green,et al.  Transcription activation by the adenovirus E1a protein , 1989, Nature.

[60]  T. Maniatis,et al.  Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-beta promoter. , 1999, Molecular cell.

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

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

[63]  P. Hogan,et al.  Transcription factors of the NFAT family: regulation and function. , 1997, Annual review of immunology.

[64]  M. Brunda,et al.  Interferons and Other Cytokines , 1997 .

[65]  M. Malim,et al.  Secreted placental alkaline phosphatase as a eukaryotic reporter gene. , 1992, Methods in enzymology.

[66]  R. Eisenman,et al.  Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. , 1991, Science.