Structure and Expression of the ATFa Gene*

The human ATFa proteins belong to the ATF/CREB family of transcription factors. We have previously shown that they mediate the transcriptional activation by the largest E1a protein and can heterodimerize with members of the Jun/Fos family. ATFa proteins have also been found tightly associated with JNK2, a stress-activated kinase. We now report on the structure of the ATFa gene, which mapped to chromosome 12 (band 12q13). Sequence analysis revealed that ATFa isoforms are generated by alternative splice donor site usage. A minimal promoter region of ∼200 base pairs was identified that retained nearly full transcriptional activity. Binding sites for potential transcription factors were delineated within a GC-rich segment by DNase I footprinting. Expression studies revealed that ATFa accumulates in the nuclei of transfected cells, and the nuclear localization signal was defined next to the leucine zipper domain. As revealed by hybridization with mouse ATFa sequences, low levels of ATFa mRNAs were ubiquitously distributed in fetal or adult mice, with enhanced expression in particular tissues, like squamous epithelia and specific brain cell layers. The possible significance of coexpression of ATFa, ATF-2, and Jun at similar sites in the brain is discussed.

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

[2]  C. Kedinger,et al.  In vivo association of ATFa with JNK/SAP kinase activities. , 1996, Oncogene.

[3]  B. Chen,et al.  ATF3 Gene , 1996, The Journal of Biological Chemistry.

[4]  R. Sidman,et al.  Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice , 1996, Nature.

[5]  F. Mitelman,et al.  Two distinct FUS breakpoint clusters in myxoid liposarcoma and acute myeloid leukemia with the translocations t(12;16) and t(16;21). , 1995, Oncogene.

[6]  D. Le Paslier,et al.  The gene coding for interferon-gamma is linked to the D12S335 and D12S313 microsatellites and to the MDM2 gene. , 1995, Genomics.

[7]  H. van Dam,et al.  Modulation of AP‐1/ATF transcription factor activity by the adenovirus‐e1a oncogene products , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  W. V. D. Van de Ven,et al.  Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas. , 1995, Cancer research.

[9]  N. Jones,et al.  ATF‐2 contains a phosphorylation‐dependent transcriptional activation domain. , 1995, The EMBO journal.

[10]  J. Woodgett,et al.  Stress-activated protein kinases bind directly to the delta domain of c-Jun in resting cells: implications for repression of c-Jun function. , 1995, Oncogene.

[11]  B. Dérijard,et al.  Transcription factor ATF2 regulation by the JNK signal transduction pathway , 1995, Science.

[12]  P. Chambon,et al.  Retinoic Acid Receptor β2 (RARβ2) Null Mutant Mice Appear Normal , 1994 .

[13]  Alcino J. Silva,et al.  Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein , 1994, Cell.

[14]  T. Boulikas.  Putative nuclear localization signals (NLS) in protein transcription factors , 1994, Journal of cellular biochemistry.

[15]  C. Kedinger,et al.  Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and modulate its transcriptional activity. , 1994, Oncogene.

[16]  J. Whelan,et al.  ATF-a0, a novel variant of the ATF/CREB transcription factor family, forms a dominant transcription inhibitor in ATF-a heterodimers. , 1994, The Journal of biological chemistry.

[17]  J. Whelan,et al.  Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines , 1993, Molecular and cellular biology.

[18]  D. Ward,et al.  Localization of the human Sp1 transcription factor gene to 12q13 by fluorescence in situ hybridization. , 1993, Genomics.

[19]  G. Thomas,et al.  EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts , 1993, Nature Genetics.

[20]  N. Mandahl,et al.  Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma , 1993, Nature.

[21]  V. Maréchal,et al.  The DNA-binding domain of two bZIP transcription factors, the Epstein-Barr virus switch gene product EB1 and Jun, is a bipartite nuclear targeting sequence , 1993, Journal of virology.

[22]  C. Kedinger,et al.  Transcriptional activation by the adenovirus larger E1a product is mediated by members of the cellular transcription factor ATF family which can directly associate with E1a , 1993, Molecular and cellular biology.

[23]  P. Sassone-Corsi,et al.  Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. , 1992, The Journal of biological chemistry.

[24]  F. Mitelman,et al.  Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11) , 1992, Genes, chromosomes & cancer.

[25]  P. Chambon,et al.  Immunodetection of multiple species of retinoic acid receptor α : evidence for phosphorylation , 1992 .

[26]  J. Fargnoli,et al.  Isolation, characterization and chromosomal localization of the human GADD153 gene. , 1992, Gene.

[27]  P. Vogt,et al.  Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Klüppel,et al.  Reporter constructs with low background activity utilizing the cat gene. , 1992, Gene.

[29]  S. Ishii,et al.  Complete putative metal finger and leucine zipper structures of CRE-BP1 are required for the E1A-induced trans-activation. , 1991, The Journal of biological chemistry.

[30]  I. Verma,et al.  Identification of a nuclear targeting sequence in the Fos protein. , 1991, Oncogene.

[31]  P. Sassone-Corsi,et al.  Differential expression of the jun family members in rat brain. , 1991, Oncogene.

[32]  H. DeLuca,et al.  The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7. , 1991, Genomics.

[33]  P. Chambon,et al.  Chromosomal assignment of retinoic acid receptor (RAR) genes in the human, mouse, and rat genomes. , 1991, Genomics.

[34]  C. Tanaka,et al.  Expression of the CRE-BP1 transcriptional regulator binding to the cyclic AMP response element in central nervous system, regenerating liver, and human tumors. , 1991, Oncogene.

[35]  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.

[36]  M. Yoshida,et al.  Cyclic AMP response element-binding protein, CRE-BP1, mediates the E1A-induced but not the Tax-induced trans-activation. , 1991, Oncogene.

[37]  T. Nagase,et al.  Promoter region of the human CRE-BP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element. , 1990, The Journal of biological chemistry.

[38]  T. Curran,et al.  Redox regulation of fos and jun DNA-binding activity in vitro. , 1990, Science.

[39]  M. Yoshida,et al.  Multiple cDNA clones encoding nuclear proteins that bind to the tax‐dependent enhancer of HTLV‐1: all contain a leucine zipper structure and basic amino acid domain. , 1990, The EMBO journal.

[40]  J. White,et al.  Synergistic activation of transcription by the human estrogen receptor bound to tandem responsive elements. , 1990, The EMBO journal.

[41]  Michael R. Green,et al.  A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein , 1990, Cell.

[42]  C. Kedinger,et al.  Isolation and characterization of two novel, closely related ATF cDNA clones from HeLa cells. , 1990, Nucleic acids research.

[43]  I. Verma,et al.  Cross-talk in signal transduction: TPA-inducible factor jun/AP-1 activates cAMP-responsive enhancer elements. , 1990, Oncogene.

[44]  N. Jones,et al.  Heterodimer formation between CREB and JUN proteins. , 1990, Oncogene.

[45]  P. Chambon,et al.  The transcriptional activation function located in the hormone‐binding domain of the human oestrogen receptor is not encoded in a single exon. , 1989, The EMBO journal.

[46]  D. Baltimore,et al.  The “initiator” as a transcription control element , 1989, Cell.

[47]  W. Biggs,et al.  A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence , 1989, Nature.

[48]  S. McKnight,et al.  The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. , 1988, Science.

[49]  C. Croce,et al.  Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13. , 1987, American journal of human genetics.

[50]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[51]  William D. Richardson,et al.  A short amino acid sequence able to specify nuclear location , 1984, Cell.

[52]  T. Osborne,et al.  HMG CoA reductase: A negatively regulated gene with unusual promoter and 5′ untranslated regions , 1984, Cell.

[53]  B. Howard,et al.  Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells , 1982, Molecular and cellular biology.

[54]  J. Banerji,et al.  Expression of a β-globin gene is enhanced by remote SV40 DNA sequences , 1981, Cell.

[55]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. Acker,et al.  Eukaryotic GST fusion vector for the study of protein-protein associations in vivo: application to interaction of ATFa with Jun and Fos. , 1995, BioTechniques.

[57]  P. Sassone-Corsi,et al.  Transcription factors responsive to cAMP. , 1995, Annual review of cell and developmental biology.

[58]  D. Demetrick,et al.  Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes. , 1994, Cytogenetics and cell genetics.

[59]  M. Montminy,et al.  The CREB family of transcription activators. , 1992 .

[60]  R. Laskey,et al.  Nuclear targeting sequences--a consensus? , 1991, Trends in biochemical sciences.

[61]  R. Berger,et al.  Chromosome mapping of the human RAS-related RAP1A, RAP1B, and RAP2 genes to chromosomes 1p12----p13, 12q14, and 13q34, respectively. , 1990, Cytogenetics and cell genetics.