2009年6月5日，北京生命科学研究所朱冰实验室在The Journal of Biological chemistry上发表题为“Heterogeneous Nuclear Ribonucleoprotein L Is a Subunit of Human KMT3a/Set2 Complex Required for H3 Lys-36 Trimethylation Activity in Vivo”的文章。该文章主要报道了人KMT3a复合物在维持体内三甲基化H3K36水平中的作用。
真核生物中，DNA的转录发生在染色质模板上。染色质的基本单位是由DNA缠绕组蛋白八聚体组成的核小体。核小体及其共价修饰能影响所在DNA的转录。
组蛋白H3第36位赖氨酸的甲基化（H3K36me）与活跃转录的基因相关。酵母中，组蛋白甲基化酶KMT3介导的H3K36甲基化招募一个组蛋白去乙酰化复合物，Rpd3s，确保了转录起始的精确性。本文报道人KMT3a（也叫HYPB或hSet2）复合物的纯化工作，和一个高等真核生物特有的亚基HnRNP-L（Heterogeneous nuclear RiboNucleoProtein L）的鉴定。KMT3a在体外单独具有组蛋白甲基化酶的能力，但是HnRNP-L在体内有重要作用。而且，虽然KMT3a在体外可以产生单、二和三甲基化产物，但是在体内针对KMT3a或HnRNP-L的RNA干涉导致H3K36三甲基化水平的整体下降，而不影响其它的修饰水平。本研究为进一步了解组蛋白修饰和转录调控提供了基础。
论文的共同第一作者袁文是北京生命科学研究所与中国农业大学联合培养的博士生，朱冰博士和纽约大学Danny Reinberg博士是论文的通讯作者。该项目由科技部863计划，美国国家健康研究所，美国国家肿瘤研究所和霍华德休斯医学研究所资助。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Biol. Chem., Vol. 284, Issue 23, 15701-15707, June 5, 2009
Heterogeneous Nuclear Ribonucleoprotein L Is a Subunit of Human KMT3a/Set2 Complex Required for H3 Lys-36 Trimethylation Activity in Vivo*
Wen Yuan?1, Jingwei Xie?1, Chengzu Long?, Hediye Erdjument-Bromage||, Xiaojun Ding?, Yong Zheng?**, Paul Tempst||, She Chen?, Bing Zhu?**2, and Danny Reinberg**3
From the From the State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100094, China, the , Graduate Program, Peking union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China, the , ?National Institute of Biological Sciences, 7 Science Park Road, Zhong Guan Cun Life Science Park, Beijing 102206, China, the , ||Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, and the , **Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York 10016
ABSTRACT
The presence of histone H3 lysine 36 methylation (H3K36me) correlates with actively transcribed genes. In yeast, histone H3K36me mediated by KMT3 (also known as Set2) recruits a histone deacetylase complex, Rpd3s, to ensure the fidelity of transcription initiation. We report the purification of human KMT3a (also known as HYPB or hSet2) complex and the identification of a novel, higher eukaryotic specific subunit, heterogeneous nuclear ribonucleoprotein L (HnRNP-L). Interestingly, although KMT3a has intrinsic activity in vitro, HnRNP-L is essential in vivo. Moreover, KMT3a generates mono-, di-, and trimethylated products in vitro, but RNA interference against KMT3a or HnRNP-L down-regulates exclusively the H3K36me3 mark in vivo.
