WT1-BASP1 对转录的抑制作用需要 BASP1 的豆蔻酰化和 PIP2 依赖性招募组蛋白去乙酰化酶。
Repression of transcription by WT1-BASP1 requires the myristoylation of BASP1 and the PIP2-dependent recruitment of histone deacetylase.
机构信息
Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA.
出版信息
Cell Rep. 2012 Sep 27;2(3):462-9. doi: 10.1016/j.celrep.2012.08.005. Epub 2012 Aug 30.
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.
摘要
Wilms 瘤 1 蛋白 WT1 是一种转录调节因子，参与细胞生长和分化。转录核心抑制因子 BASP1 与 WT1 相互作用，将 WT1 从转录激活因子转换为转录抑制因子。在这里，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 结合核 PIP2，这导致 PIP2 募集到 WT1 依赖性靶基因的启动子区域。BASP1 的豆蔻酰化和与 PIP2 的关联对于 BASP1 与 HDAC1 的相互作用是必需的，HDAC1 介导 HDAC1 募集到启动子并引发转录抑制。我们的发现揭示了豆蔻酰化在转录中的作用，以及 PIP2 通过募集组蛋白去乙酰化酶在基因特异性转录抑制中的关键作用。
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