2009年6月5日，北京生命科學研究所朱冰實驗室在The Journal of Biological chemistry上發表題為「Heterogeneous Nuclear Ribonucleoprotein L Is a Subunit of Human KMT3a/Set2 Complex Required for H3 Lys-36 Trimethylation Activity in Vivo」的文章。該文章主要報導了人KMT3a複合物在維持體內三甲基化H3K36水平中的作用。
真核生物中，DNA的轉錄發生在染色質模板上。染色質的基本單位是由DNA纏繞組蛋白八聚體組成的核小體。核小體及其共價修飾能影響所在DNA的轉錄。
組蛋白H3第36位賴氨酸的甲基化（H3K36me）與活躍轉錄的基因相關。酵母中，組蛋白甲基化酶KMT3介導的H3K36甲基化招募一個組蛋白去乙醯化複合物，Rpd3s，確保了轉錄起始的精確性。本文報導人KMT3a（也叫HYPB或hSet2）複合物的純化工作，和一個高等真核生物特有的亞基HnRNP-L（Heterogeneous nuclear RiboNucleoProtein L）的鑑定。KMT3a在體外單獨具有組蛋白甲基化酶的能力，但是HnRNP-L在體內有重要作用。而且，雖然KMT3a在體外可以產生單、二和三甲基化產物，但是在體內針對KMT3a或HnRNP-L的RNA幹涉導致H3K36三甲基化水平的整體下降，而不影響其它的修飾水平。本研究為進一步了解組蛋白修飾和轉錄調控提供了基礎。
論文的共同第一作者袁文是北京生命科學研究所與中國農業大學聯合培養的博士生，朱冰博士和紐約大學Danny Reinberg博士是論文的通訊作者。該項目由科技部863計劃，美國國家健康研究所，美國國家腫瘤研究所和霍華德休斯醫學研究所資助。（生物谷Bioon.com）
生物谷推薦原始出處：
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.