Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase
The Wilms' tumor 1 protein WT1 is a transcriptional regulator that is involved in cell growth and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and converts WT1 from a transcriptional activator to a repressor. Here, we demonstrate that the N-terminal myristoylation o...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002306 |
| _version_ | 1828310198170681344 |
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| author | Eneda Toska Hayley A. Campbell Jayasha Shandilya Sarah J. Goodfellow Paul Shore Kathryn F. Medler Stefan G.E. Roberts |
| author_facet | Eneda Toska Hayley A. Campbell Jayasha Shandilya Sarah J. Goodfellow Paul Shore Kathryn F. Medler Stefan G.E. Roberts |
| author_sort | Eneda Toska |
| collection | DOAJ |
| description | The Wilms' tumor 1 protein WT1 is a transcriptional regulator that is involved in cell growth and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and converts WT1 from a transcriptional activator to a repressor. Here, we demonstrate that the N-terminal myristoylation of BASP1 is required in order to elicit transcriptional repression at WT1 target genes. We show that myristoylated BASP1 binds to nuclear PIP2, which leads to the recruitment of PIP2 to the promoter regions of WT1-dependent target genes. BASP1's myristoylation and association with PIP2 are required for the interaction of BASP1 with HDAC1, which mediates the recruitment of HDAC1 to the promoter and elicits transcriptional repression. Our findings uncover a role for myristoylation in transcription, as well as a critical function for PIP2 in gene-specific transcriptional repression through the recruitment of histone deacetylase. |
| first_indexed | 2024-04-13T15:39:40Z |
| format | Article |
| id | doaj.art-7066041f837e47c09aa6357aefe6cc56 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T15:39:40Z |
| publishDate | 2012-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7066041f837e47c09aa6357aefe6cc562022-12-22T02:41:10ZengElsevierCell Reports2211-12472012-09-012346246910.1016/j.celrep.2012.08.005Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone DeacetylaseEneda Toska0Hayley A. Campbell1Jayasha Shandilya2Sarah J. Goodfellow3Paul Shore4Kathryn F. Medler5Stefan G.E. Roberts6Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USAFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, UKDepartment of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USAFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, UKFaculty of Life Sciences, University of Manchester, Manchester M13 9PT, UKDepartment of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USADepartment of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USAThe Wilms' tumor 1 protein WT1 is a transcriptional regulator that is involved in cell growth and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and converts WT1 from a transcriptional activator to a repressor. Here, we demonstrate that the N-terminal myristoylation of BASP1 is required in order to elicit transcriptional repression at WT1 target genes. We show that myristoylated BASP1 binds to nuclear PIP2, which leads to the recruitment of PIP2 to the promoter regions of WT1-dependent target genes. BASP1's myristoylation and association with PIP2 are required for the interaction of BASP1 with HDAC1, which mediates the recruitment of HDAC1 to the promoter and elicits transcriptional repression. Our findings uncover a role for myristoylation in transcription, as well as a critical function for PIP2 in gene-specific transcriptional repression through the recruitment of histone deacetylase.http://www.sciencedirect.com/science/article/pii/S2211124712002306 |
| spellingShingle | Eneda Toska Hayley A. Campbell Jayasha Shandilya Sarah J. Goodfellow Paul Shore Kathryn F. Medler Stefan G.E. Roberts Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase Cell Reports |
| title | Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase |
| title_full | Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase |
| title_fullStr | Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase |
| title_full_unstemmed | Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase |
| title_short | Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase |
| title_sort | repression of transcription by wt1 basp1 requires the myristoylation of basp1 and the pip2 dependent recruitment of histone deacetylase |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002306 |
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