PHD 手指蛋白 1 的 Tudor 结构域是赖氨酸 36 位三甲基化的组蛋白 H3 和赖氨酸 27 位组蛋白变体 H3t 的双重读取器。

The Tudor domain of the PHD finger protein 1 is a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t.

机构信息

Institute of Biochemistry, Stuttgart University, Pfaffenwaldring 55, 70569 Stuttgart, Germany.

Department of Biotechnology, Pondicherry University, R. V. Nagar, Kalapet, Puducherry 605014, India.

出版信息

J Mol Biol. 2014 Apr 17;426(8):1651-60. doi: 10.1016/j.jmb.2013.08.009. Epub 2013 Aug 15.

DOI:10.1016/j.jmb.2013.08.009

PMID:23954330

Abstract

PHF1 associates with the Polycomb repressive complex 2 and it was demonstrated to stimulate its H3K27-trimethylation activity. We studied the interaction of the PHF1 Tudor domain with modified histone peptides and found that it recognizes H3K36me3 and H3tK27me3 (on the histone variant H3t) and that it uses the same trimethyllysine binding pocket for the interaction with both peptides. Since both peptide sequences are very different, this result indicates that reading domains can have dual specificities. Sub-nuclear localization studies of full-length PHF1 in human HEK293 cells revealed that it co-localizes with K27me3, but not with K36me3, and that this co-localization depends on the trimethyllysine binding pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain. Our data suggest that PHF1 binds to H3tK27me3 in human chromatin, and H3t has a more general role in Polycomb regulation.

摘要

PHF1 与 Polycomb 抑制复合物 2 相关联，它被证明可以刺激其 H3K27 三甲基化活性。我们研究了 PHF1 Tudor 结构域与修饰组蛋白肽的相互作用，发现它识别 H3K36me3 和 H3tK27me3（组蛋白变体 H3t 上），并且它使用相同的三甲基赖氨酸结合口袋与这两种肽相互作用。由于这两个肽序列非常不同，这一结果表明阅读域可以具有双重特异性。在人 HEK293 细胞中全长 PHF1 的亚核定位研究表明，它与 K27me3 共定位，但不与 K36me3 共定位，并且这种共定位依赖于三甲基赖氨酸结合口袋，表明 K27me3 是 PHF1 Tudor 结构域的体内靶标。我们的数据表明，PHF1 在人类染色质中结合 H3tK27me3，并且 H3t 在 Polycomb 调控中具有更普遍的作用。