Department of Obstetrics and Gynecology, University of Texas Health Science Center in San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
EMBO Rep. 2010 Jun;11(6):438-44. doi: 10.1038/embor.2010.62. Epub 2010 May 7.
Histone methylation has a key role in oestrogen receptor (ERalpha)-mediated transactivation of genes. Proline glutamic acid and leucine-rich protein 1 (PELP1) is a new proto-oncogene that functions as an ERalpha co-regulator. In this study, we identified histone lysine demethylase, KDM1, as a new PELP1-interacting protein. These proteins, PELP1 and KDM1, were both recruited to ERalpha target genes, and PELP1 depletion affected the dimethyl histone modifications at ERalpha target genes. Dimethyl-modified histones H3K4 and H3K9 are recognized by PELP1, and PELP1 alters the substrate specificity of KDM1 from H3K4 to H3K9. Effective demethylation of dimethyl H3K9 by KDM1 requires a KDM1-ERalpha-PELP1 functional complex. These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERalpha target genes.
组蛋白甲基化在雌激素受体 (ERalpha) 介导的基因转录激活中起着关键作用。脯氨酸-谷氨酸-亮氨酸丰富蛋白 1 (PELP1) 是一种新的原癌基因，作为 ERalpha 共激活因子发挥作用。在这项研究中，我们鉴定了组蛋白赖氨酸去甲基化酶 KDM1 作为 PELP1 的新相互作用蛋白。这些蛋白质，PELP1 和 KDM1，都被招募到 ERalpha 靶基因上，并且 PELP1 的耗竭影响 ERalpha 靶基因的二甲基组蛋白修饰。二甲基化修饰的组蛋白 H3K4 和 H3K9 被 PELP1 识别，并且 PELP1 改变了 KDM1 的底物特异性，从 H3K4 到 H3K9。KDM1 对二甲基 H3K9 的有效去甲基化需要 KDM1-ERalpha-PELP1 功能复合物。这些结果表明 PELP1 是 H3 甲基化标记的读取器，并在调节 ERalpha 靶基因的组蛋白密码中起着关键作用。
