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首页> 外文期刊>Cell discovery. >MOF as an evolutionarily conserved histone crotonyltransferase and transcriptional activation by histone acetyltransferase-deficient and crotonyltransferase-competent CBP/p300
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MOF as an evolutionarily conserved histone crotonyltransferase and transcriptional activation by histone acetyltransferase-deficient and crotonyltransferase-competent CBP/p300

机译：MOF作为一种进化上保守的组蛋白巴豆酰基转移酶，并通过组蛋白乙酰转移酶缺陷和具有巴豆酰基转移酶能力的CBP / p300进行转录激活

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Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution. We provide evidence that CBP and p300 are the major HCTs in mammalian cells. Furthermore, we have generated novel CBP/p300 mutants with deficient histone acetyltransferase but competent HCT activity. These CBP/p300 mutants can substitute the endogenous CBP/p300 to enhance transcriptional activation in the cell, which correlates with enhanced promoter crotonylation and recruitment of DPF2, a selective reader for crotonylated histones. Taken together, we have identified MOF as an evolutionarily conserved HCT and provide first cellular evidence that CBP/p300 can facilitate transcriptional activation through histone acylation other than acetylation, thus supporting an emerging role for the non-acetylation type of histone acylation in transcription and possibly other chromatin-based processes.
机译：最近的研究表明，组蛋白受到各种类型的酰化作用，包括乙酰化，丙酰化和巴豆酰化。已显示CBP和p300催化多种类型的酰化反应，但在进化中不保守，这引发了有关其他酶是否存在组蛋白酰化反应以及乙酰化与其他类型酰化反应之间功能关系的问题。在这项研究中，我们专注于催化组蛋白巴豆酰化的酶，并证明在已知的组蛋白乙酰基转移酶中，MOF除了CBP和p300外，还具有组蛋白巴豆酰转移酶（HCT）活性，并且该活性在进化中得以保留。我们提供的证据表明CBP和p300是哺乳动物细胞中的主要HCT。此外，我们已经产生了具有不足的组蛋白乙酰转移酶但具有强大的HCT活性的新型CBP / p300突变体。这些CBP / p300突变体可以替代内源性CBP / p300，以增强细胞中的转录激活，这与增强的启动子巴豆酰化和DPF2（巴豆酰化组蛋白的选择性阅读器）的募集相关。综上所述，我们已经将MOF确定为进化上保守的HCT，并提供了第一个细胞证据，表明CBP / p300可以通过除乙酰化以外的组蛋白酰化促进转录激活，从而支持非乙酰化类型的组蛋白酰化在转录中的新兴作用，并可能其他基于染色质的过程。

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