组蛋白的翻译后修饰是基因表达调控中的一个关键机制。修饰发生在必需被组蛋白“阅读器”蛋白如实翻译的组合中。 对转录和染色质调控因子TRIM24的晶体结构所做的一项研究表明，它是一种独特的组蛋白“阅读器”，能够对组蛋白H3上的双标记进行组合识别。TRIM24涉及依赖于雌激素的基因的激发，在乳腺癌中异常表达。这项工作确定了染色体“阅读器”可能影响致癌作用的一个新路径。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
