10.21-OCT4综述.docVIP

表观遗传学对Oct4基因表达的调节作用 第一部分:表观遗传学(Epigenetic) 一、Histone methylation 1、Embryonic stem cells 1.1 Histone H3 lysine 4 methylation is associated with the transcriptional reprogramming efficiency of somatic nuclei by oocytes. Epigenetics Chromatin 2010,3:4.(IF=4.731) 1.1.1 实验内容: 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. This study investigated a range of histone modifications in mouse nuclei transplanted to Xenopus laevis oocyte germinal vesicles (GVs,胚泡) in order to ask whether histone modifications are changed at the nuclear or chromatin levels. 1.1.2 实验结果: ①. The transcriptional reprogramming of pluripotency genes, such as Sox2 and Oct4, takes place in transplanted nuclei from C3H 10T1/2 cells and from newly differentiated mouse embryonic stem cells (DmES). ②. 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. ③. Histone phosphorylation is increased and histone acetylation is decreased in several regulatory and gene coding regions. An increase of histone H3 lysine 4 dimethylation (H3K4me2) is seen in the regulatory regions and gene coding region of pluripotency genes in reprogrammed nuclei. ④. histone H3 lysine 4 trimethylation (H3K4me3) 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 β-globin, a gene that is not reprogrammed. ⑤. When 10T1/2 nuclei are incubated in Xenopus oocyte extracts, histone H3 serine 10 (H3S10) is strongly phosphorylated within a few hours. 1.1.3 结论: 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