2012年11月7日 訊 /生物谷BIOON/ --將成熟細(xì)胞消除其身份（核重新編程）讓它成為任何類型的細(xì)胞,，可以來修復(fù)受損的組織或更換化療后骨髓。最近諾貝爾和平獎(jiǎng)博士John B. Gurdon在2月4號(hào)的Epigenetics & Chromatin雜志上發(fā)表論文證實(shí)組蛋白分子伴侶蛋白Hira沉積的組蛋白H3.3是恢復(fù)核多能性,，使其成為多種類型細(xì)胞的關(guān)鍵。
個(gè)體所有細(xì)胞具有相同的DNA,，但隨著生物體的成熟,，這些細(xì)胞是可以編程的，能成為不同類型組織如心臟,，肺或腦,。為了要做到這一點(diǎn)，每個(gè)細(xì)胞系不同的基因或多或少會(huì)被永久關(guān)閉,。
隨著胚胎的增長(zhǎng),，細(xì)胞分裂成一定數(shù)目后，細(xì)胞就不能成為別的組織,。例如心臟細(xì)胞不能被轉(zhuǎn)換成肺組織,，肌肉細(xì)胞不能形成骨。DNA重新編程是將成熟細(xì)胞的細(xì)胞核轉(zhuǎn)移到一個(gè)受精卵中,。受精卵內(nèi)的蛋白和其他因素相互影響,，改變DNA和其他一些基因的開關(guān)，直到它成為類似于多能干細(xì)胞的DNA,。
為了了解核重編程過程,，Gurdon博士研究將小鼠核移植到青蛙的卵母細(xì)胞中。他們通過顯微注射熒光標(biāo)記的組蛋白,，讓他們能看到這些組蛋白在細(xì)胞和細(xì)胞核中的位置,。
Gurdon教授解釋說,，使用實(shí)時(shí)顯微鏡，很明顯,，10小時(shí)以后,，H3.3（組蛋白的活性基因）被移植到卵母細(xì)胞的核中表達(dá)。我們?cè)敿?xì)分析了基因Oct4,，發(fā)現(xiàn)伴隨該基因的轉(zhuǎn)錄,，H3.3被納入Oct4中。Gurdon教授的研究小組還發(fā)現(xiàn)能將H3.3并入到染色質(zhì)中的蛋白Hira,，對(duì)核重編程也是必須的,。
弗雷德·哈欽森癌癥研究中心Steven Henikoff博士評(píng)論說，操縱H3.3為徹底清除細(xì)胞的“記憶”提供了一種方法,，這樣便于產(chǎn)生一個(gè)真正的多能干細(xì)胞,。（生物谷：Bioon.com）
doi:10.1186/1756-8935-3-4
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Histone H3 lysine 4 methylation is associated with the transcriptional reprogramming efficiency of somatic nuclei by oocytes.
Murata K, Kouzarides T, Bannister AJ, Gurdon JB.
BACKGROUND: When the nuclei of mammalian somatic cells are transplanted to amphibian oocytes in the first meiotic prophase, they are rapidly induced to begin transcribing several pluripotency genes, including Sox2 and Oct4. The more differentiated the donor cells of the nuclei, the longer it takes for the pluripotency genes to be activated after the nuclear transfer to oocytes. We have used this effect in order to investigate the role of histone modifications in this example of nuclear reprogramming.
RESULTS: Reverse transcription polymerase chain reaction analysis shows that the transcriptional reprogramming of pluripotency genes, such as Sox2 and Oct4, takes place in transplanted nuclei from C3H10T1/2 cells and from newly differentiated mouse embryonic stem cells. We find that the reprogramming of 10T1/2 nuclei is accompanied by an increased phosphorylation, an increased methylation and a rapidly reduced acetylation of several amino acids in H3 and other histones. These results are obtained by the immunofluorescent staining of transplanted nuclei and by Western blot analysis. We have also used chromatin immunoprecipitation analysis to define histone modifications associated with the regulatory or coding regions of pluripotency genes in transplanted nuclei. Histone phosphorylation is increased and histone acetylation is decreased in several regulatory and gene coding regions. An increase of histone H3 lysine 4 dimethylation (H3K4 me2) is seen in the regulatory regions and gene coding region of pluripotency genes in reprogrammed nuclei. Furthermore, histone H3 lysine 4 trimethylation (H3K4 me3) is observed more strongly in the regulatory regions of pluripotency genes in transplanted nuclei that are rapidly reprogrammed than in nuclei that are reprogrammed slowly and are not seen in beta-globin, a gene that is not reprogrammed. When 10T1/2 nuclei are incubated in Xenopus oocyte extracts, histone H3 serine 10 (H3S10) is strongly phosphorylated within a few hours. Immunodepletion of Aurora B prevents this phosphorylation.
CONCLUSION: We conclude that H3K4 me2 and me3 are likely to be important for the efficient reprogramming of pluripotency genes in somatic nuclei by amphibian oocytes and that Aurora B kinase is required for H3S10 phosphorylation which is induced in transplanted somatic cell nuclei.
