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Mol Cell Biol, May 1998, p. 2729-2737, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

c-Maf Interacts with c-Myb To Regulate Transcription of an Early Myeloid Gene during Differentiation

Shrikanth P. Hegde, Alok Kumar, Cornelia Kurschner, and Linda H. Shapiro*

Departments of Experimental Oncology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Received 22 August 1997/Returned for modification 22 October 1997/Accepted 18 February 1998

The MafB transcriptional activator plays a pivotal role in regulating lineage-specific gene expression during hematopoiesis by repressing Ets-1-mediated transcription of key erythroid-specific genes in myeloid cells. To determine the effects of Maf family proteins on the transactivation of myeloid-specific genes in myeloid cells, we tested the ability of c-Maf to influence Ets-1- and c-Myb-dependent CD13/APN transcription. Expression of c-Maf in human immature myeloblastic cells inhibited CD13/APN-driven reporter gene activity (85 to 95% reduction) and required the binding of both c-Myb and Ets, but not Maf, to the promoter fragment. c-Maf's inhibition of CD13/APN expression correlates with its ability to physically associate with c-Myb. While c-Maf mRNA and protein levels remain constant during myeloid differentiation, formation of inhibitory Myb-Maf complexes was developmentally regulated, with their levels being highest in immature myeloid cell lines and markedly decreased in cell lines representing later developmental stages. This pattern matched that of CD13/APN reporter gene expression, indicating that Maf modulation of c-Myb activity may be an important mechanism for the control of gene transcription during hematopoietic cell development.

* Corresponding author. Mailing address: Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105. Phone: (901) 495-2404. Fax: (901) 495-2032. E-mail: linda.shapiro{at}stjude.org.

Mol Cell Biol, May 1998, p. 2729-2737, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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