雖然每個細胞所含的DNA是相同的，但每個細胞的分化命運卻不盡相同,。干細胞的最終分化命運不僅與DNA有關,，還與覆蓋在DNA結構上的表觀遺傳標記物有關。
最近,，UNC醫(yī)學院的研究人員發(fā)現了一種蛋白質復合體——延伸因子(elongator),，這種蛋白質復合體能夠清除精子DNA上的表觀遺傳標記物,，對胚胎發(fā)育過程形成不同類型的細胞有重要的作用。這種延伸因子或許還可通過清除表觀遺傳標記的方式再次激活腫瘤抑制基因,，從而使腫瘤細胞轉化為正常細胞。這項研究發(fā)表在1月6日Nature雜志上,。
表觀遺傳標記物是一種標記在基因組上的化學標簽,，能夠調控基因的開啟和關閉，并最終決定細胞分化的類型,。DNA甲基化即為表觀遺傳標記物的一種類型,。
在受精過程中，父系的精子的基因組發(fā)生去甲基化,，在細胞分裂之前迅速去掉甲基標簽,，而母系的卵子在這種情況下也發(fā)生被動地發(fā)生去甲基化。隨后,，受精卵重新形成一種全新的甲基化模式,。
該課題組通過使綠色熒光標記物親和連接到非甲基化DNA上，能夠在顯微鏡下觀察到整個去甲基化的過程,。研究人員敲除掉受精卵中延伸因子基因后發(fā)現,，熒光標簽將不能連接到親代的基因組中，這說明,，延伸因子對去甲基化(demethylation)很重要,。
研究人員稱，該基因的識別或將對干細胞研究十分重要,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 6 January 2010 | doi:10.1038/nature08732
A role for the elongator complex in zygotic paternal genome demethylation
Yuki Okada1,2,4, Kazuo Yamagata3, Kwonho Hong1,2, Teruhiko Wakayama3 & Yi Zhang1,2
1 Howard Hughes Medical Institute,
2 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
3 Laboratory for Genomic Reprogramming, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
4 Present address: Career-Path Promotion Unit for Young Life Scientist, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
The life cycle of mammals begins when a sperm enters an egg. Immediately after fertilization, both the maternal and paternal genomes undergo dramatic reprogramming to prepare for the transition from germ cell to somatic cell transcription programs1. One of the molecular events that takes place during this transition is the demethylation of the paternal genome2, 3. Despite extensive efforts, the factors responsible for paternal DNA demethylation have not been identified4. To search for such factors, we developed a live cell imaging system that allows us to monitor the paternal DNA methylation state in zygotes. Through short-interfering-RNA-mediated knockdown in mouse zygotes, we identified Elp3 (also called KAT9), a component of the elongator complex5, to be important for paternal DNA demethylation. We demonstrate that knockdown of Elp3 impairs paternal DNA demethylation as indicated by reporter binding, immunostaining and bisulphite sequencing. Similar results were also obtained when other elongator components, Elp1 and Elp4, were knocked down. Importantly, injection of messenger RNA encoding the Elp3 radical SAM domain mutant, but not the HAT domain mutant, into MII oocytes before fertilization also impaired paternal DNA demethylation, indicating that the SAM radical domain is involved in the demethylation process. Our study not only establishes a critical role for the elongator complex in zygotic paternal genome demethylation, but also indicates that the demethylation process may be mediated through a reaction that requires an intact radical SAM domain.
