C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements.
Members of the C/EBP family of basic-leucine zipper (bZip) transcription factors form heterodimers and bind to the CAAT box and other sequence-related enhancer motifs. Using a 32P-labeled protein probe consisting of the bZip domain of C/EBP beta, we isolated a clone encoding C/EBP-related ATF (C/ATF), a bZip protein that heterodimerizes with C/EBP-like proteins but belongs to the CREB/ATF family. C/ATF homodimers do not bind to typical C/EBP DNA sites. Instead they bind to palindromic cAMP response elements such as that of the somatostatin gene. In addition, C/ATF-C/EBP beta heterodimers bind to a subclass of asymmetric cAMP response elements exemplified by those in the phosphoenolpyruvate carboxykinase and proenkephalin genes. Transient transfection studies indicate that interactions between C/ATF and C/EBP beta are the basis for a functional cross talk between these two families of transcription factors that may be important for the integration of hormonal and developmental stimuli that determine the expression of subsets of genes in specific cellular phenotypes.
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston 02114.
M
M
Vallejo
D
D
Ron
C P
CP
Miller
J F
JF
Habener
D016475:3T3 Cells; D051701:Activating Transcription Factor 4; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D016350:Leucine Zippers; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
C081452:Atf4 protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D015534:Trans-Activators; D014157:Transcription Factors; D051701:Activating Transcription Factor 4