Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene
The 85-kb breast cancer-associated gene BRCA1 is an established tumor suppressor gene, but its regulation is poorly understood. We demonstrate by gene conformation analysis in both human cell lines and mouse mammary tissue that gene loops are imposed on BRCA1 between the promoter, introns, and termi...
| Main Authors: | , , , |
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| Format: | Journal article |
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National Academy of Sciences
2008
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| _version_ | 1797089710174109696 |
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| author | Tan-Wong, S French, J Proudfoot, N Brown, M |
| author_facet | Tan-Wong, S French, J Proudfoot, N Brown, M |
| author_sort | Tan-Wong, S |
| collection | OXFORD |
| description | The 85-kb breast cancer-associated gene BRCA1 is an established tumor suppressor gene, but its regulation is poorly understood. We demonstrate by gene conformation analysis in both human cell lines and mouse mammary tissue that gene loops are imposed on BRCA1 between the promoter, introns, and terminator region. Significantly, association between the BRCA1 promoter and terminator regions change upon estrogen stimulation and during lactational development. Loop formation is transcription-dependent, suggesting that transcriptional elongation plays an active role in BRCA1 loop formation. We show that the BRCA1 terminator region can suppress estrogen-induced transcription and so may regulate BRCA1 expression. Significantly, BRCA1 promoter and terminator interactions vary in different breast cancer cell lines, indicating that defects in BRCA1 chromatin structure may contribute to dysregulated expression of BRCA1 seen in breast tumors. |
| first_indexed | 2024-03-07T03:07:59Z |
| format | Journal article |
| id | oxford-uuid:b335c7b7-c7f3-48b1-b4ba-52eef5560405 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:07:59Z |
| publishDate | 2008 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:b335c7b7-c7f3-48b1-b4ba-52eef55604052022-03-27T04:17:25ZDynamic interactions between the promoter and terminator regions of the mammalian BRCA1 geneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b335c7b7-c7f3-48b1-b4ba-52eef5560405Symplectic Elements at OxfordNational Academy of Sciences2008Tan-Wong, SFrench, JProudfoot, NBrown, MThe 85-kb breast cancer-associated gene BRCA1 is an established tumor suppressor gene, but its regulation is poorly understood. We demonstrate by gene conformation analysis in both human cell lines and mouse mammary tissue that gene loops are imposed on BRCA1 between the promoter, introns, and terminator region. Significantly, association between the BRCA1 promoter and terminator regions change upon estrogen stimulation and during lactational development. Loop formation is transcription-dependent, suggesting that transcriptional elongation plays an active role in BRCA1 loop formation. We show that the BRCA1 terminator region can suppress estrogen-induced transcription and so may regulate BRCA1 expression. Significantly, BRCA1 promoter and terminator interactions vary in different breast cancer cell lines, indicating that defects in BRCA1 chromatin structure may contribute to dysregulated expression of BRCA1 seen in breast tumors. |
| spellingShingle | Tan-Wong, S French, J Proudfoot, N Brown, M Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title | Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title_full | Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title_fullStr | Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title_full_unstemmed | Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title_short | Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene |
| title_sort | dynamic interactions between the promoter and terminator regions of the mammalian brca1 gene |
| work_keys_str_mv | AT tanwongs dynamicinteractionsbetweenthepromoterandterminatorregionsofthemammalianbrca1gene AT frenchj dynamicinteractionsbetweenthepromoterandterminatorregionsofthemammalianbrca1gene AT proudfootn dynamicinteractionsbetweenthepromoterandterminatorregionsofthemammalianbrca1gene AT brownm dynamicinteractionsbetweenthepromoterandterminatorregionsofthemammalianbrca1gene |