Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements
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-report...
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Published in | Cell growth & differentiation Vol. 7; no. 10; pp. 1383 - 1392 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.10.1996
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Subjects | |
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Abstract | 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. |
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AbstractList | 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. |
Author | PAVLIK, K KAUFMAN, R. E ANTHONY, B FRIDAY, E DECASTRO, C CHEN, Y VANDENBARK, G. R |
Author_xml | – sequence: 1 givenname: G. R surname: VANDENBARK fullname: VANDENBARK, G. R organization: Departments of Medicine, Section of Hematology-Oncology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, United States – sequence: 2 givenname: Y surname: CHEN fullname: CHEN, Y organization: Departments of Medicine, Section of Hematology-Oncology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, United States – sequence: 3 givenname: E surname: FRIDAY fullname: FRIDAY, E organization: Departments of Medicine, Section of Hematology-Oncology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, United States – sequence: 4 givenname: K surname: PAVLIK fullname: PAVLIK, K organization: Departments of Medicine, Section of Biochemistry/Molecular Biology, Shreveport, Louisiana 71130-3932, United States – sequence: 5 givenname: B surname: ANTHONY fullname: ANTHONY, B organization: Departments of Medicine, Section of Biochemistry/Molecular Biology, Shreveport, Louisiana 71130-3932, United States – sequence: 6 givenname: C surname: DECASTRO fullname: DECASTRO, C organization: Department of Medicine, Division of Hematology-Oncology, Duke University Medical Center, Durham, North Carolina 27710, United States – sequence: 7 givenname: R. E surname: KAUFMAN fullname: KAUFMAN, R. E organization: Department of Medicine, Division of Hematology-Oncology, Duke University Medical Center, Durham, North Carolina 27710, United States |
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Keywords | Human Regulatory sequence Transcription Transcription promoter C-Onc gene |
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Snippet | The c-kit proto-oncogene is expressed in several tissues during development. To understand the mechanisms controlling the expression of this gene, we... |
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SubjectTerms | Base Sequence Biological and medical sciences Cell Line Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Fundamental and applied biological sciences. Psychology Gene Expression Regulation Humans Molecular and cellular biology Molecular genetics Molecular Sequence Data Oncogenes Promoter Regions, Genetic - genetics Proto-Oncogene Proteins c-kit - genetics Transcription, Genetic Transcription. Transcription factor. Splicing. Rna processing |
Title | Complex regulation of human c-kit transcription by promoter repressors, activators, and specific myb elements |
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