Crosstalk between CARM1 methylation and CBP acetylation on histone H3
Crosstalk between CARM1 methylation and CBP acetylation on histone H3
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DOI：
10.1016/s0960-9822(02)01387-8
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发表时间：
2002-12-23
期刊：
影响因子：
9.2
通讯作者：
Kouzarides, T
中科院分区：
文献类型：
--
作者：
Daujat, S;Bauer, UM;Kouzarides, T
背景：组蛋白修饰模式的动态变化，如乙酰化、磷酸化、甲基化和泛素化，被认为主要通过影响染色质结构和非组蛋白调节因子与染色质的相互作用，为基因表达的正确调控提供了一个密码。最近的研究表明，在转录过程中组蛋白修饰之间存在相互作用。CBP/p300乙酰化酶和CARM1甲基转移酶可以正向调节雌激素应答基因的表达，但在体内尚未证实染色质上赖氨酸乙酰化和精氨酸甲基化之间存在串音。结果：通过观察组蛋白H3的体内修饰模式，在雌激素刺激pS2启动子后，我们发现精氨酸甲基化发生在H3乙酰化之后。雌激素刺激后15分钟内，CBP与染色质结合，K18发生乙酰化。在这些事件之后，K23发生乙酰化，CARM1与染色质结合，R17发生甲基化。在体内，外源性CBP的表达足以驱动CARM1与染色质和R17甲基化的关联，而乙酰化酶缺陷的CBP突变体无法诱导这些事件。乙酰化和精氨酸甲基化之间的合作机制来自于K18和K23的乙酰化，而不是K14，将重组CARM1束缚在H3尾部，并使其成为更有效的精氨酸甲基转移酶。结论：这些结果揭示了在雌激素调节的转录过程中乙酰化和精氨酸甲基化的有序和相互依赖的沉积，并为组蛋白修饰在基因表达中的组合作用提供了支持。
Background: Dynamic changes in the modification pattern of histones, such as acetylation, phosphorylation, methylation, and ubiquitination, are thought to provide a code for the correct regulation of gene expression mostly by affecting chromatin structure and interactions of non-histone regulatory factors with chromatin. Recent studies have suggested the existence of an interplay between histone modifications during transcription. The CBP/p300 acetylase and the CARM1 methyltransferase can positively regulate the expression of estrogen-responsive genes, but the existence of a crosstalk between lysine acetylation and arginine methylation on chromatin has not yet been established in vivo.Results: By following the in vivo pattern of modifications on histone H3, following estrogen stimulation of the pS2 promoter, we show that arginine methylation follows prior acetylation of H3. Within 15 min after estrogen stimulation, CBP is bound to chromatin, and acetylation of K18 takes place. Following these events, K23 is acetylated, CARM1 associates with chromatin, and methylation at R17 takes place. Exogenous expression of CBP is sufficient to drive the association of CARM1 with chromatin and methylation of R17 in vivo, whereas an acetylase-deficient CBP mutant is unable to induce these events. A mechanism for the observed cooperation between acetylation and arginine methylation comes from the finding that acetylation at K18 and K23, but not K14, tethers recombinant CARM1 to the H3 tail and allows it to act as a more efficient arginine methyltransferase.Conclusion: These results reveal an ordered and interdependent deposition of acetylation and arginine methylation during estrogen-regulated transcription and provide support for a combinatorial role of histone modifications in gene expression.