Abstract

We have characterized the role of c-Myb and B-Myb in the regulation of human type I collagen alpha2 chain gene expression in fibroblastic cells. We have identified four Myb-binding sites (MBSs) in the promoter. Transactivation assays on wild type and mutant promoter-reporter constructs demonstrated that c-Myb, but not B-Myb, can transactivate the human type I collagen alpha 2 chain gene promoter via the MBS-containing region. Electrophoretic mobility shift assay experiments showed that c-Myb specifically binds to each of the four MBS; however, the mutagenesis of site MBS-4 completely inhibited transactivation by c-Myb, at least in the full-length promoter. In agreement with these results, c-myb(-/-) mouse embryo fibroblasts (MEFs) showed a selective lack of expression of type I collagen alpha 2 chain gene but maintained the expression of fibronectin and type III collagen. Furthermore, transforming growth factor-beta induced type I collagen alpha 2 chain gene expression in c-myb(-/-) MEFs, implying that the transforming growth factor-beta signaling pathway is maintained and that the absence of COL1A2 gene expression in c-myb(-/-) MEFs is a direct consequence of the lack of c-Myb. The demonstration of the importance of c-Myb in the regulation of the type I collagen alpha 2 chain gene suggests that uncontrolled expression of c-Myb could be an underlying mechanism in the pathogenesis of several fibrotic disorders.

Highlights

  • The myb oncogene family is composed of c-myb, A-myb, and B-myb genes, each encoding a distinct nuclear protein that displays transcription factor activity [1]

  • Transactivation of the COL1A2 promoter by c-Myb and B-Myb has been investigated in human fibroblasts and human fibroblast cell lines, and the regions of the promoter that are critical for Myb-mediated transactivation have been determined

  • By using the computerized software MatInspector version 2.2, we have analyzed the DNA sequence of the promoter of the human type I collagen ␣2 chain (COL1A2-P), and we found four putative Myb-binding sites (MBSs)

Read more

Summary

Introduction

The myb oncogene family is composed of c-myb, A-myb, and B-myb genes, each encoding a distinct nuclear protein that displays transcription factor activity [1].

Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call