title: Repression of transcription by WT1-BASP1 requires the myristoylation of BASP1 and the PIP2-dependent recruitment of histone deacetylase.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Eneda
authors.initials: E
authors.lastname: Toska
authors.forename: Hayley A
authors.initials: HA
authors.lastname: Campbell
authors.forename: Jayasha
authors.initials: J
authors.lastname: Shandilya
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Goodfellow
authors.forename: Paul
authors.initials: P
authors.lastname: Shore
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Medler
authors.forename: Stefan G E
authors.initials: SG
authors.lastname: Roberts
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D054878:Lipoylation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C104089:BASP1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D012097:Repressor Proteins; D025721:WT1 Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1