組蛋白的翻譯后修飾是基因表達(dá)調(diào)控中的一個(gè)關(guān)鍵機(jī)制,。修飾發(fā)生在必需被組蛋白“閱讀器”蛋白如實(shí)翻譯的組合中,。 對(duì)轉(zhuǎn)錄和染色質(zhì)調(diào)控因子TRIM24的晶體結(jié)構(gòu)所做的一項(xiàng)研究表明，它是一種獨(dú)特的組蛋白“閱讀器”,，能夠?qū)M蛋白H3上的雙標(biāo)記進(jìn)行組合識(shí)別,。TRIM24涉及依賴于雌激素的基因的激發(fā)，在乳腺癌中異常表達(dá),。這項(xiàng)工作確定了染色體“閱讀器”可能影響致癌作用的一個(gè)新路徑,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09542
TRIM24 links a non-canonical histone signature to breast cancer
Wen-Wei Tsai,Zhanxin Wang,Teresa T. Yiu,Kadir C. Akdemir,Weiya Xia,Stefan Winter,Cheng-Yu Tsai,Xiaobing Shi,Dirk Schwarzer,William Plunkett,Bruce Aronow,Or Gozani,Wolfgang Fischle,Mien-Chie Hung,Dinshaw J. Patel& Michelle Craig Barton
Recognition of modified histone species by distinct structural domains within ‘reader’ proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.
