Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF.
For a gene to be transcribed in a tissue-specific fashion, expression must be achieved in the appropriate cell type and also be prevented in other tissues. As an approach to understanding the regulation of tissue-specific gene expression, we have analyzed the requirements for melanocyte-specific exp...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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1994
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| _version_ | 1797077274433945600 |
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| author | Yavuzer, U Goding, C |
| author_facet | Yavuzer, U Goding, C |
| author_sort | Yavuzer, U |
| collection | OXFORD |
| description | For a gene to be transcribed in a tissue-specific fashion, expression must be achieved in the appropriate cell type and also be prevented in other tissues. As an approach to understanding the regulation of tissue-specific gene expression, we have analyzed the requirements for melanocyte-specific expression of the tyrosinase-related protein 1 (TRP-1) promoter. Positive regulation of TRP-1 expression is mediated by both an octamer-binding motif and an 11-bp element, termed the M box, which is conserved between the TRP-1 and other melanocyte-specific promoters. We show here that, consistent with its ability to activate transcription in a non-tissue-specific fashion, the M box binds the basic-helix-loop-helix factor USF in vitro. With the use of a combination of site-directed mutagenesis and chimeric promoter constructs, additional elements involved in regulating TRP-1 expression were identified. These include the TATA region, which appears to contribute to the melanocyte specificity of the TRP-1 promoter. Mutational analysis also identified two repressor elements, one at the start site, the other located at -240, which function both in melanoma and nonmelanoma cells. In addition, a melanocyte-specific factor, MSF, binds to sites which overlap both repressor elements, with substitution mutations demonstrating that binding by MSF is not required for repression. Although a functional role for MSF has not been unequivocally determined, the location of its binding sites leads us to speculate that it may act as a melanocyte-specific antirepressor during transcription of the endogenous TRP-1 gene. |
| first_indexed | 2024-03-07T00:15:35Z |
| format | Journal article |
| id | oxford-uuid:7abdb351-9510-4cd9-b031-a8e0a016d5e3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:15:35Z |
| publishDate | 1994 |
| record_format | dspace |
| spelling | oxford-uuid:7abdb351-9510-4cd9-b031-a8e0a016d5e32022-03-26T20:45:54ZMelanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7abdb351-9510-4cd9-b031-a8e0a016d5e3EnglishSymplectic Elements at Oxford1994Yavuzer, UGoding, CFor a gene to be transcribed in a tissue-specific fashion, expression must be achieved in the appropriate cell type and also be prevented in other tissues. As an approach to understanding the regulation of tissue-specific gene expression, we have analyzed the requirements for melanocyte-specific expression of the tyrosinase-related protein 1 (TRP-1) promoter. Positive regulation of TRP-1 expression is mediated by both an octamer-binding motif and an 11-bp element, termed the M box, which is conserved between the TRP-1 and other melanocyte-specific promoters. We show here that, consistent with its ability to activate transcription in a non-tissue-specific fashion, the M box binds the basic-helix-loop-helix factor USF in vitro. With the use of a combination of site-directed mutagenesis and chimeric promoter constructs, additional elements involved in regulating TRP-1 expression were identified. These include the TATA region, which appears to contribute to the melanocyte specificity of the TRP-1 promoter. Mutational analysis also identified two repressor elements, one at the start site, the other located at -240, which function both in melanoma and nonmelanoma cells. In addition, a melanocyte-specific factor, MSF, binds to sites which overlap both repressor elements, with substitution mutations demonstrating that binding by MSF is not required for repression. Although a functional role for MSF has not been unequivocally determined, the location of its binding sites leads us to speculate that it may act as a melanocyte-specific antirepressor during transcription of the endogenous TRP-1 gene. |
| spellingShingle | Yavuzer, U Goding, C Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title | Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title_full | Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title_fullStr | Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title_full_unstemmed | Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title_short | Melanocyte-specific gene expression: role of repression and identification of a melanocyte-specific factor, MSF. |
| title_sort | melanocyte specific gene expression role of repression and identification of a melanocyte specific factor msf |
| work_keys_str_mv | AT yavuzeru melanocytespecificgeneexpressionroleofrepressionandidentificationofamelanocytespecificfactormsf AT godingc melanocytespecificgeneexpressionroleofrepressionandidentificationofamelanocytespecificfactormsf |