PHF20 Readers Link Methylation of Histone H3K4 and p53 with H4K16 Acetylation.
PHF20 Readers Link Methylation of Histone H3K4 and p53 with H4K16 Acetylation.
复制标题
DOI：
10.1016/j.celrep.2016.09.056
复制
发表时间：
2016-10-18
期刊：
影响因子：
8.8
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
--
作者：
Klein BJ;Wang X;Cui G;Yuan C;Botuyan MV;Lin K;Lu Y;Wang X;Zhao Y;Bruns CJ;Mer G;Shi X;Kutateladze TG
PHF20是赖氨酸乙酰转移酶复合体MOF(第一次雄性缺失)-NSL(非特异性致死)的核心成分，它产生主要的表观遗传标记H4K16ac，是转录调控和DNA修复所必需的。PHF20在复合体中的作用仍然难以捉摸。在这里，我们报告了PHF20中甲基化阅读器之间的功能耦合。我们发现PHF20的植物同源结构域(PHD)手指识别组蛋白H3(H3K4me2)的二甲基化赖氨酸4，并代表了一个选择这种修饰的本地读者的例子。生化和结构分析有助于解释这种选择性和PHF20中的另一位读者Tudor2对二甲基化p53的偏好。PHD手指与H3K4me2的结合是组蛋白乙酰化、在靶基因积累PHF20和转录激活所必需的。总之，我们的发现建立了PHF20介导的MOF组蛋白乙酰转移酶(HAT)、P53和H3K4me2之间的独特联系，并建议了一种快速传播H4K16ac丰富的开放染色质的模型。Klein等人。发现PHF20的PhD指是H3K4me2的阅读器，它是负责H4K16乙酰化的MOF-NSL帽子复合体的核心亚单位。作者表明，与H3K4me2结合是依赖PHF20的组蛋白乙酰化、靶基因激活以及癌细胞生长和存活所必需的。
PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first)-NSL (non-specific lethal) that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD) finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents an example of a native reader that selects for this modification. Biochemical and structural analyses help to explain this selectivity and the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a unique PHF20-mediated link between MOF histone acetyltransferase (HAT), p53, and H3K4me2, and suggest a model for rapid spreading of H4K16ac-enriched open chromatin. Klein et al. find that the PHD finger of PHF20, a core subunit of the MOF-NSL HAT complex responsible for H4K16 acetylation, is a reader of H3K4me2. The authors show that binding to H3K4me2 is required for PHF20-dependent histone acetylation, target gene activation, and cancer cell growth and survival.
登录
查看更多内容
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
Botuyan, MV;Mer, G;Arrowsmith, CH
通讯作者：
Arrowsmith, CH
影响因子：
8.8
作者：
Klein BJ;Piao L;Xi Y;Rincon-Arano H;Rothbart SB;Peng D;Wen H;Larson C;Zhang X;Zheng X;Cortazar MA;Peña PV;Mangan A;Bentley DL;Strahl BD;Groudine M;Li W;Shi X;Kutateladze TG
通讯作者：
Kutateladze TG
影响因子：
16.8
作者：
Cui, Gaofeng;Park, Sungman;Badeaux, Aimee I.;Kim, Donghwa;Lee, Joseph;Thompson, James R.;Yan, Fei;Kaneko, Satoshi;Yuan, Zengqiang;Botuyan, Maria Victoria;Bedford, Mark T.;Cheng, Jin Q.;Mer, Georges
通讯作者：
Mer, Georges
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH