Journal of Leukocyte Biology
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(Journal of Leukocyte Biology. 2003;73:263-272.)
© 2003 by Society for Leukocyte Biology

Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML-1 transcription factor

B. Guyot and G. Mouchiroud

Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Université Claude Bernard Lyon-1, Villeurbanne Cedex, France

Correspondence: G. Mouchiroud, Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Université Claude Bernard Lyon-1, Bâtiment Gregor Mendel, 16 rue Raphael Dubois, 69622 Villeurbanne Cedex, France. E-mail: gmouchir{at}biomserv.univ-lyon1.fr

Monocytic adaptor (Mona, also called Gads) is a molecular adaptor implicated in T cell activation and macrophage differentiation. The objective of this study was to identify elements regulating specific expression of Mona/Gads in human T cell and myelomonocytic cell lines. We first confirmed that the -2000 to +150 genomic region relative to the Mona gene transcription start site is sufficient to direct specific reporter gene expression in T cell lines, Jurkat, and MOLT-4 and in the immature myeloid cell lines, KG1a and RC2A. Deletion analysis and electrophoresis mobility shift assay identified several cis regulatory elements: overlapping initiator sequences, one interferon response factor-2 (IRF-2)-binding site at position -154, one GC box recognized by Sp1 and Sp3 at position -52, and two acute myeloid leukemia (AML)-1 binding sites at positions -70 and -13. Site-directed mutagenesis experiments indicated a key role of AML-1 for driving Mona expression in T cells and myeloid cells, and involvement of Sp1/Sp3 and IRF-2 transcription factors to modulate Mona expression in a cell-specific manner.

Key Words: hematopoiesis • signaling molecule • transcriptional regulation




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