近日,美国芝加哥大学Ben May癌症研究所赵英明教授与上海药物所叶阳研究员研究者们合作,发表在国际顶尖杂志《细胞》Cell上关于组蛋白翻译后修饰系统研究的论文“Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification,”被《细胞》杂志编辑选为2011年5篇研究亮点之一,2011年上海药物所与赵英明教授合作,组建化学蛋白质组学研究中心,开展高效、可靠的蛋白修饰调控酶靶标发现及生物标记物鉴定的新技术研究工作,以期为新药研究探索提供更为快速和有效的途径。中心成立后,谭敏佳博士、赵英明教授即开展相关研究工作,并取得重要进展。
在2011年一年内,《细胞》杂志共发表了三百多篇原创性论文。上述论文在众多一流工作中脱颖而出,被《细胞》杂志编辑选为2011年“表观遗传”(epigenome)领域的研究亮点,认为此项研究工作所发现的67个新组蛋白修饰位点不但极大丰富了染色质的表观遗传标记的内容(vocabulary of chromatin),而且发现了一种全新的、与调控精子发育密切相关的组蛋白表观遗传修饰-赖氨酸巴豆酰化。这些新的组蛋白修饰的发现为以后的细胞生理机制及疾病发生机制的研究提供了重要基石。此项研究一经发表后,也马上被《自然评论遗传学》杂志和由全世界1万多名生物医学领域国际顶尖教授组成的“Faculty of 1000”学术网站(f1000.com/13276967)列为研究亮点。(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.