Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage d...Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different（P〈0.01） between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01）, which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.展开更多
Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 ...Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 gene polymorphisms are associated with prostate cancer remain unclear. In this study, we aimed to determine whether the presence of IL-18 and OCT4 polymorphisms were associated with size, grade, tumor, nodes and metastasis(TNM) stage, or survival in patients with prostate cancer.Methods Polymorphisms in OCT4 and IL-18 genes were evaluated to determine susceptibility to prostate cancer in 120 patients. A control group consisted of 125 Chinese participants. Genotyping was performed using TaqMan allelic discrimination assays, and statistical analysis was performed using SPSS. Results No association was found between OCT4 and IL-18 gene polymorphisms and prostate cancer susceptibility. For OCT4 AA and IL-18-607 CC genotypes, there was a significant association with higher tumor grade(P = 0.03 and P = 0.025) and stage(P = 0.04 and P = 0.001). The OCT4 and IL-18-137 GG genotype was correlated with higher tumor grade(P = 0.028) and stage(P = 0.008). Furthermore, OCT4 AA was significantly more frequent in patients with lymph node metastasis(P = 0.02) and distant metastasis(P = 0.01). The Cox proportional hazard model showed that tumor grade and stage grouping were independent prognostic factors but IL-18 and OCT4 polymorphisms were not. Conclusion The OCT4 gene may have a profound effect on prostate cancer risk. Polymorphism variants in the IL-18(IL-18-607 and IL-18-137) and OCT4 genes may be associated with poor prognoses for individuals with prostate cancer.展开更多
为探讨多能性转录因子OCT4和SOX2在昆明小鼠(Mus musculus)2-细胞胚胎发育过程中与2-细胞胚胎阻滞发生的相关性,本研究应用实时荧光定量PCR技术检测了小鼠卵母细胞及在M16培养液中培养的不同发育阶段体外受精胚Oct4和Sox2基因的表达,并...为探讨多能性转录因子OCT4和SOX2在昆明小鼠(Mus musculus)2-细胞胚胎发育过程中与2-细胞胚胎阻滞发生的相关性,本研究应用实时荧光定量PCR技术检测了小鼠卵母细胞及在M16培养液中培养的不同发育阶段体外受精胚Oct4和Sox2基因的表达,并利用实时荧光定量PCR和免疫荧光技术比较了2-细胞胚、2-细胞阻滞胚和4-细胞胚的OCT4和SOX2的表达与定位。采用ANOVA对实验所得的数据进行分析,P<0.05被认为是具有显著性差异。研究结果显示,2-细胞胚只有24.8%发育成4-细胞胚,75.2%的2-细胞胚发生了阻滞。Sox2和Oct4的m RNA在MⅡ期卵母细胞、原核胚、2-细胞胚、4-细胞胚、桑椹胚和囊胚中都有表达。Oct4 m RNA的表达水平在4-细胞胚显著高于2-细胞胚和2-细胞阻滞胚(P<0.05),Sox2 m RNA的表达水平在2-细胞胚显著高于2-细胞阻滞胚和4-细胞胚(P<0.05),而后两者之间没有差异(P<0.05)。OCT4蛋白在2-细胞胚和4-细胞胚中与核共定位,但在2-细胞阻滞胚中弥散存在于胞质中。SOX2蛋白在以上3类胚胎中始终定位于细胞核。上述结果提示,转录因子OCT4和SOX2的表达和定位与小鼠2-细胞胚胎发育阻滞相关,母源性SOX2表达的维持对胚胎合子基因组激活(ZGA)的发生具有重要作用,母源性OCT4的异常定位可能影响了合子基因组激活相关基因的激活,而合子中Oct4的表达影响合子基因组激活后胚胎的发育。展开更多
The MLL/SET family of histone H3 lysine 4 methyltransferases form enzyme complexes with core subunits ASH2L, WDR5, RbBP5, and DPY-30 （often abbreviated WRAD）, and are responsible for global histone H3 iysine 4 methy...The MLL/SET family of histone H3 lysine 4 methyltransferases form enzyme complexes with core subunits ASH2L, WDR5, RbBP5, and DPY-30 （often abbreviated WRAD）, and are responsible for global histone H3 iysine 4 methylation, a hallmark of actively transcribed chromatin in mammalian cells. Accordingly, the function of these proteins is required for a wide variety of processes including stem cell differentiation, cell growth and division, body segmentation, and hematopoiesis. While most work on MLL-WRAD has focused on the function this core complex in histone methylation, recent studies indicate that MLL-WRAD proteins interact with a variety of other proteins and IncRNAs and can localize to cellular organelles beyond the nucleus. In this review, we focus on the recently described activities and interacting partners of MLL-WRAD both inside and outside the nucleus.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province, China (2014JQ3104)the National Natural Science Foundation of China (31000655)China Postdoctoral Science Foundation funded project (2014M560809)
文摘Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different（P〈0.01） between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01）, which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.
基金Supported by grants from the China Postdoctoral Science Foundation(No.2014M139951)the Science and Technology Project of Nantong,Jiangsu Province(No.MS22016043)
文摘Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 gene polymorphisms are associated with prostate cancer remain unclear. In this study, we aimed to determine whether the presence of IL-18 and OCT4 polymorphisms were associated with size, grade, tumor, nodes and metastasis(TNM) stage, or survival in patients with prostate cancer.Methods Polymorphisms in OCT4 and IL-18 genes were evaluated to determine susceptibility to prostate cancer in 120 patients. A control group consisted of 125 Chinese participants. Genotyping was performed using TaqMan allelic discrimination assays, and statistical analysis was performed using SPSS. Results No association was found between OCT4 and IL-18 gene polymorphisms and prostate cancer susceptibility. For OCT4 AA and IL-18-607 CC genotypes, there was a significant association with higher tumor grade(P = 0.03 and P = 0.025) and stage(P = 0.04 and P = 0.001). The OCT4 and IL-18-137 GG genotype was correlated with higher tumor grade(P = 0.028) and stage(P = 0.008). Furthermore, OCT4 AA was significantly more frequent in patients with lymph node metastasis(P = 0.02) and distant metastasis(P = 0.01). The Cox proportional hazard model showed that tumor grade and stage grouping were independent prognostic factors but IL-18 and OCT4 polymorphisms were not. Conclusion The OCT4 gene may have a profound effect on prostate cancer risk. Polymorphism variants in the IL-18(IL-18-607 and IL-18-137) and OCT4 genes may be associated with poor prognoses for individuals with prostate cancer.
文摘为探讨多能性转录因子OCT4和SOX2在昆明小鼠(Mus musculus)2-细胞胚胎发育过程中与2-细胞胚胎阻滞发生的相关性,本研究应用实时荧光定量PCR技术检测了小鼠卵母细胞及在M16培养液中培养的不同发育阶段体外受精胚Oct4和Sox2基因的表达,并利用实时荧光定量PCR和免疫荧光技术比较了2-细胞胚、2-细胞阻滞胚和4-细胞胚的OCT4和SOX2的表达与定位。采用ANOVA对实验所得的数据进行分析,P<0.05被认为是具有显著性差异。研究结果显示,2-细胞胚只有24.8%发育成4-细胞胚,75.2%的2-细胞胚发生了阻滞。Sox2和Oct4的m RNA在MⅡ期卵母细胞、原核胚、2-细胞胚、4-细胞胚、桑椹胚和囊胚中都有表达。Oct4 m RNA的表达水平在4-细胞胚显著高于2-细胞胚和2-细胞阻滞胚(P<0.05),Sox2 m RNA的表达水平在2-细胞胚显著高于2-细胞阻滞胚和4-细胞胚(P<0.05),而后两者之间没有差异(P<0.05)。OCT4蛋白在2-细胞胚和4-细胞胚中与核共定位,但在2-细胞阻滞胚中弥散存在于胞质中。SOX2蛋白在以上3类胚胎中始终定位于细胞核。上述结果提示,转录因子OCT4和SOX2的表达和定位与小鼠2-细胞胚胎发育阻滞相关,母源性SOX2表达的维持对胚胎合子基因组激活(ZGA)的发生具有重要作用,母源性OCT4的异常定位可能影响了合子基因组激活相关基因的激活,而合子中Oct4的表达影响合子基因组激活后胚胎的发育。
文摘The MLL/SET family of histone H3 lysine 4 methyltransferases form enzyme complexes with core subunits ASH2L, WDR5, RbBP5, and DPY-30 （often abbreviated WRAD）, and are responsible for global histone H3 iysine 4 methylation, a hallmark of actively transcribed chromatin in mammalian cells. Accordingly, the function of these proteins is required for a wide variety of processes including stem cell differentiation, cell growth and division, body segmentation, and hematopoiesis. While most work on MLL-WRAD has focused on the function this core complex in histone methylation, recent studies indicate that MLL-WRAD proteins interact with a variety of other proteins and IncRNAs and can localize to cellular organelles beyond the nucleus. In this review, we focus on the recently described activities and interacting partners of MLL-WRAD both inside and outside the nucleus.
