2012年11月7日 讯 /生物谷BIOON/ --将成熟细胞消除其身份（核重新编程）让它成为任何类型的细胞，可以来修复受损的组织或更换化疗后骨髓。最近诺贝尔和平奖博士John B. Gurdon在2月4号的Epigenetics & Chromatin杂志上发表论文证实组蛋白分子伴侣蛋白Hira沉积的组蛋白H3.3是恢复核多能性，使其成为多种类型细胞的关键。
个体所有细胞具有相同的DNA，但随着生物体的成熟，这些细胞是可以编程的，能成为不同类型组织如心脏，肺或脑。为了要做到这一点，每个细胞系不同的基因或多或少会被永久关闭。
随着胚胎的增长，细胞分裂成一定数目后，细胞就不能成为别的组织。例如心脏细胞不能被转换成肺组织，肌肉细胞不能形成骨。DNA重新编程是将成熟细胞的细胞核转移到一个受精卵中。受精卵内的蛋白和其他因素相互影响，改变DNA和其他一些基因的开关，直到它成为类似于多能干细胞的DNA。
为了了解核重编程过程，Gurdon博士研究将小鼠核移植到青蛙的卵母细胞中。他们通过显微注射荧光标记的组蛋白，让他们能看到这些组蛋白在细胞和细胞核中的位置。
Gurdon教授解释说，使用实时显微镜，很明显，10小时以后，H3.3（组蛋白的活性基因）被移植到卵母细胞的核中表达。我们详细分析了基因Oct4，发现伴随该基因的转录，H3.3被纳入Oct4中。Gurdon教授的研究小组还发现能将H3.3并入到染色质中的蛋白Hira，对核重编程也是必须的。
弗雷德·哈钦森癌症研究中心Steven Henikoff博士评论说，操纵H3.3为彻底清除细胞的“记忆”提供了一种方法，这样便于产生一个真正的多能干细胞。（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.
