近日,,美國(guó)芝加哥大學(xué)Ben May癌癥研究所趙英明教授與上海藥物所葉陽研究員研究者們合作,,發(fā)表在國(guó)際頂尖雜志《細(xì)胞》Cell上關(guān)于組蛋白翻譯后修飾系統(tǒng)研究的論文“Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification,”被《細(xì)胞》雜志編輯選為2011年5篇研究亮點(diǎn)之一,,2011年上海藥物所與趙英明教授合作,,組建化學(xué)蛋白質(zhì)組學(xué)研究中心,開展高效,、可靠的蛋白修飾調(diào)控酶靶標(biāo)發(fā)現(xiàn)及生物標(biāo)記物鑒定的新技術(shù)研究工作,,以期為新藥研究探索提供更為快速和有效的途徑。中心成立后,,譚敏佳博士,、趙英明教授即開展相關(guān)研究工作,并取得重要進(jìn)展,。
在2011年一年內(nèi),,《細(xì)胞》雜志共發(fā)表了三百多篇原創(chuàng)性論文。上述論文在眾多一流工作中脫穎而出,,被《細(xì)胞》雜志編輯選為2011年“表觀遺傳”(epigenome)領(lǐng)域的研究亮點(diǎn),,認(rèn)為此項(xiàng)研究工作所發(fā)現(xiàn)的67個(gè)新組蛋白修飾位點(diǎn)不但極大豐富了染色質(zhì)的表觀遺傳標(biāo)記的內(nèi)容(vocabulary of chromatin),而且發(fā)現(xiàn)了一種全新的,、與調(diào)控精子發(fā)育密切相關(guān)的組蛋白表觀遺傳修飾-賴氨酸巴豆?;_@些新的組蛋白修飾的發(fā)現(xiàn)為以后的細(xì)胞生理機(jī)制及疾病發(fā)生機(jī)制的研究提供了重要基石,。此項(xiàng)研究一經(jīng)發(fā)表后,,也馬上被《自然評(píng)論遺傳學(xué)》雜志和由全世界1萬多名生物醫(yī)學(xué)領(lǐng)域國(guó)際頂尖教授組成的“Faculty of 1000”學(xué)術(shù)網(wǎng)站(f1000.com/13276967)列為研究亮點(diǎn)。(生物谷Bioon.com)
doi:10.1016/j.cell.2011.08.008
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Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification
Minjia Tan, Hao Luo, Sangkyu Lee, Fulai Jin, Jeong Soo Yang, Emilie Montellier, Thierry Buchou, Zhongyi Cheng, Sophie Rousseaux, Nisha Rajagopal, Zhike Lu, Zhen Ye, Qin Zhu, Joanna Wysocka, Yang Ye, Saadi Khochbin, Bing Ren, Yingming Zhao
Highlights Identification of 67 novel histone marks including 28 lysine crotonylation sites Verification of Kcr as a novel histone mark Kcr is a robust indicator of active cellular genes Kcr is likely an important histone mark for male germ cell differentiation Summary We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells.