A dual activation mechanism for Myb-responsive genes in myelomonocytic cells.
The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the transformation of myelomonocytic cells by avian myeloblastosis virus (AMV). v-Myb is thought to exert its biological effects by deregulating the expression of specific target genes. Here we have used DNaseI hypersensitive site mapping and reporter gene assays to study the activation of three Myb target genes--mim-1, the lysozyme gene and the C/EBPbeta gene--all of which are activated by Myb in myelomonocytic cells but not in other hematopoietic lineages. We have found that these genes are activated by Myb via more than one cis-regulatory region. Our data suggest that all three genes are activated by Myb by dual mechanisms involving the promoters as well as enhancers. Using a cell line that expresses an estrogen-inducible v-Myb/estrogen receptor fusion protein we have also determined the effect of Myb on the expression of the C/EBPalpha gene. Our results show that C/EBPalpha expression is down-regulated by v-Myb. Thus, v-Myb affects the expression of two C/EBP family members in opposite directions.
Yamkamon
Vichanan
V
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, D-48149 Münster, Germany.
Ivanova
Olga
O
Braas
Daniel
D
Chayka
Olesya
O
Patmasiriwat
Pimpicha
P
Klempnauer
Karl-Heinz
KH
D000818:Animals; D009189:Avian Myeloblastosis Virus; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics* / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D002461:Cell Line, Transformed; D002645:Chickens; D017930:Genes, Reporter; D020570:Genes, myb; D009113:Muramidase / Q000235:genetics*; D020626:Oncogene Proteins v-myb / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D020626:Oncogene Proteins v-myb; D014157:Transcription Factors; D009113:Muramidase