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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing
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Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing

机译:涉及H3 S28磷酸化和K27乙酰化的组蛋白编码途径激活转录并拮抗多梳沉默

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摘要

Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activator. Targeting of this H3 kinase to the endogenous c-fos promoter is sufficient to activate its expression without the need of upstream signaling. Moreover, targeting MSK1 to the a-globin promoter induces H3 S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Importantly, we discovered a mechanism whereby H3 S28 phosphorylation not only displaces binding of the polycomb-repressive complexes, but it also induces a methyl-acetylation switch of the adjacent K27 residue. Our findings show that signal transduction activation can directly regulate polycomb silencing through a specific histone code-mediated mechanism.
机译:组蛋白H3磷酸化是将信号转导途径与基因调控耦合的关键步骤。为了具体评估H3磷酸化的转录调控功能,我们开发了一种体内靶向方法,发现H3激酶MSK1是直接有效的转录激活因子。将该H3激酶靶向内源性c-fos启动子足以激活其表达,而无需上游信号传导。而且,将MSK1靶向a-珠蛋白启动子可诱导H3 S28磷酸化并重新激活该多梳沉默基因的表达。重要的是,我们发现了一种机制,其中H3 S28磷酸化不仅置换了多梳抑制复合物的结合,而且还诱导了相邻K27残基的甲基乙酰化开关。我们的发现表明,信号转导激活可以通过特定的组蛋白编码介导的机制直接调节多梳沉默。

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