Journal
CELL REPORTS
Volume 2, Issue 3, Pages 462-469Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.08.005
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Funding
- Biotechnology and Biological Sciences Research Council
- National Institute of General Medical Sciences [1R01GM098609]
- Cancer Research UK [C1356/A6630]
- National Science Foundation [NSF0917893]
- Association for International Cancer Research
- Wellcome Trust [WT061207MA]
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [0917893] Funding Source: National Science Foundation
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0923133] Funding Source: National Science Foundation
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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.
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