Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins.
The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene expression profiles, and whether they cooperate or compete in regulating the same promoters. Here, recombinant adenoviruses were used to express each protein in human mammary cells, and then microarray assays were used to assess global changes in gene expression. Each Myb protein induced a unique and specific set of changes, displaying activities far more complex than revealed by standard reporter gene assays. These results have important implications for the roles of various Myb proteins in normal and transformed human cells, for regulatory pathways that might modify their activities and for the importance of acquired mutations that may qualitatively alter their functions in tumors.
Rushton
John J
JJ
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, USA.
Davis
Lisa M
LM
Lei
Wanli
W
Mo
Xianming
X
Leutz
Achim
A
Ness
Scott A
SA
D000256:Adenoviridae / Q000235:genetics; D001940:Breast / Q000166:cytology / Q000502:physiology; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004847:Epithelial Cells; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007633:Keratins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088831:MYBL1 protein, human; C064352:MYBL2 protein, human; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D007633:Keratins