Selective targeting of histone methylation
Selective targeting of histone methylation
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DOI：
10.4161/cc.10.3.14705
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发表时间：
2011-02-01
期刊：
影响因子：
4.3
通讯作者：
Benevolenskaya, Elizaveta V.
中科院分区：
文献类型：
--
作者：
Islam, Abul B. M. M. K.;Richter, William F.;Benevolenskaya, Elizaveta V.
组蛋白被多种组蛋白修饰酶进行翻译后修饰，进而影响基因表达。迄今为止，该领域的大部分工作都集中在这些酶的遗传、生化和结构表征上。最新的全基因组方法提供了对体内组蛋白修饰酶的特异性招募的见解，从而了解建立差异表达模式的机制。在这里，我们重点关注参与两个对比组蛋白标记、组蛋白 H3 赖氨酸 4 (H3K4) 甲基化和组蛋白 H3 赖氨酸 27 (H3K27) 甲基化的酶的招募机制。我们描述了它们的结合位点的分布，并表明不同组蛋白修饰蛋白的募集可以是协调的、相反的或交替的。具体而言，在 KDM5A 水平降低的细胞中，H3K4 组蛋白去甲基化酶 KDM5A 的基因组位点可与其同源物 KDM5B 接触。目前有关 H3K4/H3K27 修饰酶招募的数据表明，形成的蛋白质复合物以连续和时间的方式靶向，但额外的、仍未知的相互作用有助于靶向特异性。
Histones are post-translationally modified by multiple histone-modifying enzymes, which in turn influences gene expression. Much of the work in the field to date has focused on genetic, biochemical and structural characterization of these enzymes. The most recent genome-wide methods provide insights into specific recruitment of histone-modifying enzymes in vivo and, therefore, onto mechanisms of establishing a differential expression pattern. Here we focus on the recruitment mechanisms of the enzymes involved in the placement of two contrasting histone marks, histone H3 lysine 4 (H3K4) methylation and histone H3 lysine 27 (H3K27) methylation. We describe distribution of their binding sites and show that recruitment of different histone-modifying proteins can be coordinated, opposed or alternating. Specifically, genomic sites of the H3K4 histone demethylase KDM5A become accessible to its homolog KDM5B in cells with a lowered KDM5A level. The currently available data on recruitment of H3K4/H3K27 modifying enzymes suggests that the formed protein complexes are targeted in a sequential and temporal manner, but that additional, still unknown, interactions contribute to targeting specificity.