The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms.
The BASP1 transcriptional corepressor modifies chromatin through lipid-dependent and lipid-independent mechanisms.
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DOI：
10.1016/j.isci.2022.104796
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发表时间：
2022-08-19
期刊：
影响因子：
5.8
通讯作者：
Roberts, Stefan G. E.
中科院分区：
文献类型：
--
作者：
Moorhouse, Alexander J.;Loats, Amy E.;Medler, Kathryn F.;Roberts, Stefan G. E.
转录辅阻遏物 BASP1 需要 N 末端肉豆蔻酰化才能通过与核脂质相互作用来发挥其活性和功能。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 去除活性组蛋白修饰 H3K9ac 和 H3K4me3 需要 BASP1 的 N 端肉豆蔻酰化。相比之下，BASP1 放置抑制性组蛋白修饰 H3K27me3 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，并诱导染色质可及性的广泛变化。我们发现 ~50% 的 BASP1 靶基因表现出脂化依赖性染色质压缩和转录抑制。我们的结果表明，BASP1 在组蛋白修饰和转录抑制中引发脂质依赖性和脂质非依赖性功能。据此，我们发现BASP1的肿瘤抑制活性也部分依赖于其肉豆蔻酰化。需要 BASP1 的肉豆蔻酰化来去除活性 H3K9ac 和 H3K4me3 H3K27me3 的 BASP1 依赖性放置不需要 BASP1 的肉豆蔻酰化 BASP1 的肿瘤抑制活性依赖于肉豆蔻酰化 BASP1 的脂化调节染色质可及性 分子生物学；分子遗传学；组学；转录组学
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. Myristoylation of BASP1 is required to remove active H3K9ac and H3K4me3 BASP1-dependent placement of H3K27me3 does not require the myristoylation of BASP1 The tumor suppressor activity of BASP1 is myristoylation dependent Lipidation of BASP1 modulates chromatin accessibility Molecular biology; Molecular Genetics; Omics; Transcriptomics
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
4.4
作者：
Garcia-Gil, Mercedes;Albi, Elisabetta
通讯作者：
Albi, Elisabetta
影响因子：
4.6
作者：
Gao, Yankun;Toska, Eneda;Medler, Kathryn F.
通讯作者：
Medler, Kathryn F.
影响因子：
14.9
作者：
Davis AP;Grondin CJ;Johnson RJ;Sciaky D;McMorran R;Wiegers J;Wiegers TC;Mattingly CJ
通讯作者：
Mattingly CJ
DOI：
10.1042/bj20101734
发表时间：
2011-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Goodfellow SJ;Rebello MR;Toska E;Zeef LA;Rudd SG;Medler KF;Roberts SG
通讯作者：
Roberts SG