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 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.

肾母细胞瘤1蛋白WT1是一种参与细胞生长和分化的转录调节因子。转录辅阻遏物BASP1与WT1相互作用，并将WT1从转录激活因子转变为阻遏因子。在此，我们证明BASP1的N端豆蔻酰化对于在WT1靶基因上引发转录抑制是必需的。我们表明，豆蔻酰化的BASP1与核内磷脂酰肌醇 - 4,5 - 二磷酸（PIP2）结合，这导致PIP2被招募到WT1依赖性靶基因的启动子区域。BASP1的豆蔻酰化以及与PIP2的结合对于BASP1与组蛋白去乙酰化酶1（HDAC1）的相互作用是必需的，这种相互作用介导了HDAC1向启动子的招募并引发转录抑制。我们的研究结果揭示了豆蔻酰化在转录中的作用，以及PIP2通过招募组蛋白去乙酰化酶在基因特异性转录抑制中的关键功能。