The BASP1 transcriptional repressor modifies chromatin through lipid-dependent and lipid-independent mechanisms
The BASP1 transcriptional repressor modifies chromatin through lipid-dependent and lipid-independent mechanisms
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BASP1 转录阻遏蛋白通过脂质依赖性和脂质非依赖性机制修饰染色质
DOI：
10.1101/2022.02.15.480538
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Moorhouse A
中科院分区：
文献类型：
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作者：
Moorhouse A
转录辅阻遏子BASP1需要N-末端的肉豆蔻酰化作用，通过与核脂的相互作用来实现其活性和功能。在这里，我们确定了BASP1脂化在组蛋白修饰和染色质可及性调节中的作用。我们发现，BASP1去掉活性的组蛋白修饰H3K9ac和H3K4me3需要BASP1的N端肉豆蔻酰化。相反，BASP1对抑制性组蛋白修饰H3K27me3的放置不需要BASP1脂化。RNA-seq和ATAC-seq分析发现，BASP1调节多种转录因子的活性，并导致染色质可及性的广泛变化。我们发现，∼中50%的靶基因表现出脂化依赖的染色质紧致和转录抑制。我们的结果表明，BASP1在组蛋白修饰和转录抑制中既有脂依赖功能，也有脂非依赖功能。与此相一致，我们发现BASP1的抑瘤活性也部分依赖于其肉豆蔻酰化作用。
The transcriptional corepressor BASP1 requires N-terminal myristoylation for its activity and functions through interactions with nuclear lipids. Here we determine the role of BASP1 lipidation in histone modification and the modulation of chromatin accessibility. We find that the removal of the active histone modifications H3K9ac and H3K4me3 by BASP1 requires the N-terminal myristoylation of BASP1. In contrast, the placement of the repressive histone modification, H3K27me3, by BASP1 does not require BASP1 lipidation. RNA-seq and ATAC-seq analysis finds that BASP1 regulates the activity of multiple transcription factors and induces extensive changes in chromatin accessibility. We find that ∼50% of BASP1 target genes show lipidation-dependent chromatin compaction and transcriptional repression. Our results suggest that BASP1 elicits both lipid-dependent and lipid-independent functions in histone modification and transcriptional repression. In accordance with this, we find that the tumor suppressor activity of BASP1 is also partially dependent on its myristoylation.