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Volume 271, Number 47, Issue of November 22, 1996 pp. 29589-29598
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Structure and Expression of the ATFa Gene

(Received for publication, June 18, 1996)

Jean Goetz , Bruno Chatton , Marie-Geneviève Mattei and Claude Kedinger

From the Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, F-67404 Illkirch Cedex Communauté Urbaine de Strasbourg, France and the  Faculté de Médecine de la Timone, INSERM U-406, Boulevard Jean Moulin, 13385 Marseille Cedex, France

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.

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