Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.
The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-g...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
1995
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| _version_ | 1826284935320698880 |
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| author | Pondel, MD Murphy, S Pearson, L Craddock, C Proudfoot, N |
| author_facet | Pondel, MD Murphy, S Pearson, L Craddock, C Proudfoot, N |
| author_sort | Pondel, MD |
| collection | OXFORD |
| description | The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1. |
| first_indexed | 2024-03-07T01:21:19Z |
| format | Journal article |
| id | oxford-uuid:9072de61-367c-4f7d-9410-6cbb93e6d212 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:21:19Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:9072de61-367c-4f7d-9410-6cbb93e6d2122022-03-26T23:11:38ZSp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9072de61-367c-4f7d-9410-6cbb93e6d212EnglishSymplectic Elements at Oxford1995Pondel, MDMurphy, SPearson, LCraddock, CProudfoot, NThe 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1. |
| spellingShingle | Pondel, MD Murphy, S Pearson, L Craddock, C Proudfoot, N Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title | Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title_full | Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title_fullStr | Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title_full_unstemmed | Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title_short | Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity. |
| title_sort | sp1 functions in a chromatin dependent manner to augment human alpha globin promoter activity |
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