Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription
Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription
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MOZ 串联 PHD 指对未修饰 H3R2 和乙酰化 H3K14 的组合读出揭示了 HOXA9 转录的调控机制
DOI：
10.1101/gad.188359.112
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发表时间：
2012-06-15
影响因子：
10.5
通讯作者：
Shi, Yunyu
中科院分区：
文献类型：
--
作者：
Qiu, Yu;Liu, Lei;Shi, Yunyu
组蛋白乙酰化是基因转录的标志。作为一种组蛋白乙酰转移酶，单核细胞白血病锌指蛋白在HOX基因表达以及胚胎和出生后发育中起重要作用。在体内，MoZ与其他亚基形成四聚体复合体，包括几个具有调节功能的染色质结合模块。本文报道了人MoZ的串联PHD(植物同源结构域)指(PHD12)在游离态的溶液结构和与H3K14ac多肽形成的1.47埃晶体结构，揭示了未修饰的R2和乙酰化K14在组蛋白H3上识别的结构基础。染色质免疫沉淀(ChIP)和RT-PCR检测结果表明，PHD12促进了MoZ基因在HOXA9基因启动子区域的定位，从而促进了启动子区域周围的H3乙酰化，进一步上调了HOXA9基因的mRNA水平。综上所述，我们的发现表明，PHD12对H3R2/K14ac的组合读出可能代表了一种重要的表观遗传调控机制，该机制调控转录，并提供了MoZ复合体和组蛋白H3修饰之间的串扰线索。
Histone acetylation is a hallmark for gene transcription. As a histone acetyltransferase, MOZ (monocytic leukemia zinc finger protein) is important for HOX gene expression as well as embryo and postnatal development. In vivo, MOZ forms a tetrameric complex with other subunits, including several chromatin-binding modules with regulatory functions. Here we report the solution structure of the tandem PHD (plant homeodomain) finger (PHD12) of human MOZ in a free state and the 1.47 angstrom crystal structure in complex with H3K14ac peptide, which reveals the structural basis for the recognition of unmodified R2 and acetylated K14 on histone H3. Moreover, the results of chromatin immunoprecipitation (ChIP) and RT-PCR assays indicate that PHD12 facilitates the localization of MOZ onto the promoter locus of the HOXA9 gene, thereby promoting the H3 acetylation around the promoter region and further up-regulating the HOXA9 mRNA level. Taken together, our findings suggest that the combinatorial readout of the H3R2/K14ac by PHD12 might represent an important epigenetic regulatory mechanism that governs transcription and also provide a clue of cross-talk between the MOZ complex and histone H3 modifications.