The carbonic anhydrase I locus contains a c-Myb target promoter and modulates differentiation of murine erythroleukemia cells.
The Myb proto-oncogene encodes a transcription factor (c-Myb) that is essential for normal hematopoiesis and is thought to regulate hematopoietic cell proliferation and differentiation by regulating expression of specific target genes. We identify the mouse erythroid-specific carbonic anhydrase I promoter (CAIe) as a target of c-Myb activity and demonstrate that Myb activity is critical for carbonic anhydrase I (CAI) expression in C19 MEL cells. CAI expression is downregulated when MEL cells differentiate in response to MEnT or treatment with N, N-hexamethylene bisacetamide (HMBA). Coexpression of GATA-1 with c-Myb results in synergistic activation of transcription from the CAIe promoter and both transcription factors interact with the CAIe promoter in vivo. We identify a novel 20 bp sequence in the CAIe promoter that is sufficient to mediate synergistic activation of the CAIe promoter by c-Myb and GATA-1. c-Myb and GATA-1 interact with this DNA sequence suggesting that c-Myb and GATA-1 may be contained in a complex that interacts with this region of the CAIe promoter. Forced expression of CAI delayed HMBA-induced differentiation of MEL cells and maintained them in a proliferating state. These data strongly suggest that CAI is a c-Myb target and is involved in regulating MEL cell proliferation and differentiation.
Chen
J
J
Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA 22908-0734, USA.
Kremer
C S
CS
Bender
T P
TP
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D024401:Carbonic Anhydrase I / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D050982:GATA1 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D050982:GATA1 Transcription Factor; D020598:Proto-Oncogene Proteins c-myb; D024401:Carbonic Anhydrase I; C014026:hexamethylene bisacetamide