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Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements.

Publication ,  Journal Article
Vandenbark, GR; Chen, Y; Friday, E; Pavlik, K; Anthony, B; deCastro, C; Kaufman, RE
Published in: Cell Growth Differ
October 1996

The c-kit proto-oncogene is expressed in several tissues during development. To understand the mechanisms controlling the expression of this gene, we characterized the human c-kit promoter. Expression is controlled transcriptionally. The 5'-flanking DNA was used to make promoter deletion-reporter constructs that were tested in cells that were either positive or negative for endogenous c-Kit. The results demonstrate that DNA, to at least position -4100, directs transcription well in both positive and negative cells. Addition of DNA from position -4100 to -5500 causes a reduction in expression to near-basal levels in c-Kit-negative cells but has little effect in c-Kit-positive cells. The DNA from -4100 to -5500 was tested for repressor function. It inhibits transcription from some heterologous promoters in c-Kit-negative cells. Likewise, this segment inhibits transcription from the homologous proximal promoter in a cell-specific manner, but the entire promoter is necessary for complete repression in c-Kit-negative cells. Two Myb binding motifs were also identified, and their role in regulating transcription was examined by mutation and functional testing. One, MYB1, acts as a partial repressor, whereas the other, MYB2, is a positive element that appears essential for expression. Binding proteins to both sites were characterized by several methods. MYB1 binds and responds functionally to c-Myb, but MYB2 does not. The results of these studies indicate that the regulation of c-kit transcription is complex, involving interactions among several activators and repressors.

Duke Scholars

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

October 1996

Volume

7

Issue

10

Start / End Page

1383 / 1392

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Mas
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Oncogenes
  • Molecular Sequence Data
  • Humans
  • Gene Expression Regulation
  • Developmental Biology
 

Citation

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Vandenbark, G. R., Chen, Y., Friday, E., Pavlik, K., Anthony, B., deCastro, C., & Kaufman, R. E. (1996). Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements. Cell Growth Differ, 7(10), 1383–1392.
Vandenbark, G. R., Y. Chen, E. Friday, K. Pavlik, B. Anthony, C. deCastro, and R. E. Kaufman. “Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements.Cell Growth Differ 7, no. 10 (October 1996): 1383–92.
Vandenbark GR, Chen Y, Friday E, Pavlik K, Anthony B, deCastro C, et al. Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements. Cell Growth Differ. 1996 Oct;7(10):1383–92.
Vandenbark, G. R., et al. “Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements.Cell Growth Differ, vol. 7, no. 10, Oct. 1996, pp. 1383–92.
Vandenbark GR, Chen Y, Friday E, Pavlik K, Anthony B, deCastro C, Kaufman RE. Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements. Cell Growth Differ. 1996 Oct;7(10):1383–1392.

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

October 1996

Volume

7

Issue

10

Start / End Page

1383 / 1392

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Mas
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Oncogenes
  • Molecular Sequence Data
  • Humans
  • Gene Expression Regulation
  • Developmental Biology