2009年6月5日,，北京生命科學(xué)研究所朱冰實(shí)驗(yàn)室在The Journal of Biological chemistry上發(fā)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(bào)道了人KMT3a復(fù)合物在維持體內(nèi)三甲基化H3K36水平中的作用,。
真核生物中,，DNA的轉(zhuǎn)錄發(fā)生在染色質(zhì)模板上。染色質(zhì)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(jià)修飾能影響所在DNA的轉(zhuǎn)錄,。
組蛋白H3第36位賴氨酸的甲基化（H3K36me）與活躍轉(zhuǎn)錄的基因相關(guān)。酵母中,，組蛋白甲基化酶KMT3介導(dǎo)的H3K36甲基化招募一個(gè)組蛋白去乙?；瘡?fù)合物，Rpd3s,，確保了轉(zhuǎn)錄起始的精確性,。本文報(bào)道人KMT3a（也叫HYPB或hSet2）復(fù)合物的純化工作，和一個(gè)高等真核生物特有的亞基HnRNP-L（Heterogeneous nuclear RiboNucleoProtein L）的鑒定,。KMT3a在體外單獨(dú)具有組蛋白甲基化酶的能力,，但是HnRNP-L在體內(nèi)有重要作用。而且,，雖然KMT3a在體外可以產(chǎn)生單,、二和三甲基化產(chǎn)物，但是在體內(nèi)針對(duì)KMT3a或HnRNP-L的RNA干涉導(dǎo)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(jìn)一步了解組蛋白修飾和轉(zhuǎn)錄調(diào)控提供了基礎(chǔ)。
論文的共同第一作者袁文是北京生命科學(xué)研究所與中國(guó)農(nóng)業(yè)大學(xué)聯(lián)合培養(yǎng)的博士生,，朱冰博士和紐約大學(xué)Danny Reinberg博士是論文的通訊作者,。該項(xiàng)目由科技部863計(jì)劃，美國(guó)國(guó)家健康研究所，美國(guó)國(guó)家腫瘤研究所和霍華德休斯醫(yī)學(xué)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.
