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1.
X-Chromosome inactivation in cloned mouse embryos 总被引：2，自引：0，他引：2
Eggan K Akutsu H Hochedlinger K Rideout W Yanagimachi R Jaenisch R 《Science (New York, N.Y.)》2000,290(5496):1578-1581
To study whether cloning resets the epigenetic differences between the two X chromosomes of a somatic female nucleus, we monitored X inactivation in cloned mouse embryos. Both X chromosomes were active during cleavage of cloned embryos, followed by random X inactivation in the embryo proper. In the trophectoderm (TE), X inactivation was nonrandom with the inactivated X of the somatic donor being chosen for inactivation. When female embryonic stem cells with two active X chromosomes were used as donors, random X inactivation was seen in the TE and embryo. These results demonstrate that epigenetic marks can be removed and reestablished on either X chromosome during cloning. Our results also suggest that the epigenetic marks imposed on the X chromosomes during gametogenesis, responsible for normal imprinted X inactivation in the TE, are functionally equivalent to the marks imposed on the chromosomes during somatic X inactivation. 相似文献
2.
Reactivation of the paternal X chromosome in early mouse embryos 总被引：2，自引：0，他引：2
Mak W Nesterova TB de Napoles M Appanah R Yamanaka S Otte AP Brockdorff N 《Science (New York, N.Y.)》2004,303(5658):666-669
It is generally accepted that paternally imprinted X inactivation occurs exclusively in extraembryonic lineages of mouse embryos, whereas cells of the embryo proper, derived from the inner cell mass (ICM), undergo only random X inactivation. Here we show that imprinted X inactivation, in fact, occurs in all cells of early embryos and that the paternal X is then selectively reactivated in cells allocated to the ICM. This contrasts with more differentiated cell types where X inactivation is highly stable and generally irreversible. Our observations illustrate that an important component of genome plasticity in early development is the capacity to reverse heritable gene silencing decisions. 相似文献
3.
4.
Percec I Plenge RM Nadeau JH Bartolomei MS Willard HF 《Science (New York, N.Y.)》2002,296(5570):1136-1139
X chromosome inactivation is the silencing mechanism eutherian mammals use to equalize the expression of X-linked genes between males and females early in embryonic development. In the mouse, genetic control of inactivation requires elements within the X inactivation center (Xic) on the X chromosome that influence the choice of which X chromosome is to be inactivated in individual cells. It has long been posited that unidentified autosomal factors are essential to the process. We have used chemical mutagenesis in the mouse to identify specific factors involved in X inactivation and report two genetically distinct autosomal mutations with dominant effects on X chromosome choice early in embryogenesis. 相似文献
5.
非编码KNAXist介导的X染色体失活是表观遗传研究的一个典范,该系统能使一整条染色体变为异染状态。从Xist与X染色体计数、失活的选择、失活的起始和失活的维持等方面综述了其分子机制。 相似文献
6.
Epigenetic reprogramming in plant and animal development 总被引：1，自引：0，他引：1
Epigenetic modifications of the genome are generally stable in somatic cells of multicellular organisms. In germ cells and early embryos, however, epigenetic reprogramming occurs on a genome-wide scale, which includes demethylation of DNA and remodeling of histones and their modifications. The mechanisms of genome-wide erasure of DNA methylation, which involve modifications to 5-methylcytosine and DNA repair, are being unraveled. Epigenetic reprogramming has important roles in imprinting, the natural as well as experimental acquisition of totipotency and pluripotency, control of transposons, and epigenetic inheritance across generations. Small RNAs and the inheritance of histone marks may also contribute to epigenetic inheritance and reprogramming. Reprogramming occurs in flowering plants and in mammals, and the similarities and differences illuminate developmental and reproductive strategies. 相似文献
7.
Jain M Arvanitis C Chu K Dewey W Leonhardt E Trinh M Sundberg CD Bishop JM Felsher DW 《Science (New York, N.Y.)》2002,297(5578):102-104
Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model for MYC-induced tumorigenesis to demonstrate that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes. Subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. Thus, brief MYC inactivation appears to cause epigenetic changes in tumor cells that render them insensitive to MYC-induced tumorigenesis. These results raise the possibility that transient inactivation of MYC may be an effective therapy for certain cancers. 相似文献
8.
A small-RNA perspective on gametogenesis, fertilization, and early zygotic development 总被引：1，自引：0，他引：1
Transient populations of cis- and trans-acting small RNAs have recently emerged as key regulators of extensive epigenetic changes taking place during periconception, which encompasses gametogenesis, fertilization, and early zygotic development. These small RNAs are not only important to maintain genome integrity in the gametes and zygote, but they also actively contribute to assessing the compatibility of parental genomes at fertilization and to promoting long-term memory of the zygotic epigenetic landscape by affecting chromatin. Striking parallels exist in the biogenesis and modus operandi of these molecules among diverse taxa, unraveling universal themes of small-RNA-mediated epigenetic reprogramming during sexual reproduction. 相似文献
9.
Female infertility represents a major challenge for improving the production efficiency in the dairy industry. Historically, fertility has declined whereas milk yield has increased tremendously due to intensive genetic selection. In vivo evidence reveals about 60% pregnancy loss takes place during the first month following fertilization. Meanwhile, early embryo development is significant for somatic cell nuclear transfer in cattle as a large proportion of cloned embryos fail to develop beyond peri-implantation stage. Oocyte quality is of utmost importance for the early embryo to develop to term for both fertilized and cloned embryos. Epigenetic reprogramming is a key process occurring after fertilization and critical roles of epigenetic modifiers during preimplantation development are now clear. Incomplete epigenetic reprogramming is believed to be a major limitation to cloning efficiency. Treatment of cloned embryos with epigenetic modifying drugs (e.g., Trichostatin A) could greatly improve cloning efficiency in both mice and cattle. Recently, the rapid progress in high-throughput sequencing technologies has enabled detailed deciphering of the molecular mechanisms underlying these events. The robust efficiency of genomic editing tools also presents an alternative approach to the functional annotation of genes critical to early development. 相似文献
10.
Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific methylation of the inactive X chromosome has been demonstrated at promoter CpG islands, but the overall pattern of methylation on the active X(Xa) and inactive X (Xi) chromosomes is unknown. We performed allele-specific analysis of more than 1000 informative loci along the human X chromosome. The Xa displays more than two times as much allele-specific methylation as Xi. This methylation is concentrated at gene bodies, affecting multiple neighboring CpGs. Before X inactivation, all of these Xa gene body-methylated sites are biallelically methylated. Thus, a bipartite methylation-demethylation program results in Xa-specific hypomethylation at gene promoters and hypermethylation at gene bodies. These results suggest a relationship between global methylation and expression potentiality. 相似文献
11.
Role of histone H3 lysine 27 methylation in X inactivation 总被引：1，自引：0，他引：1
Plath K Fang J Mlynarczyk-Evans SK Cao R Worringer KA Wang H de la Cruz CC Otte AP Panning B Zhang Y 《Science (New York, N.Y.)》2003,300(5616):131-135
The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi. 相似文献
12.
肌肉发育相关LncRNA的研究进展 总被引：3，自引：1，他引：2
生长发育性状是受遗传和环境因素共同作用和/或相互作用的复杂性状,尽管利用全基因组关联研究可分析基因组上全部基因,筛选出与某类性状关联的SNP,但很难综合评价某个基因对其确切的作用。寻找与生长发育相关的精准基因是育种研究的目标之一。长链非编码RNA(long noncoding RNA,LncRNA)在细胞增殖分化、个体发育、信号转导、干细胞维持、代谢等几乎所有重要生命活动中发挥关键的调控作用,在表观遗传水平、转录水平及转录后水平等方面具有控制基因表达的作用,与多种重大疾病的发生密切相关。LncRNA是一类长度大于200个nt,且不表现出蛋白质编码潜能的RNAs,通过多种机制发挥生物学功能,参与染色质修饰、X染色体沉默以及基因组印记、转录干扰、转录激活、核内运输等多种重要调控过程,涉及表观遗传调控、转录调控及转录后调控等多个层面。深入探讨LncRNA调控生肌因子进而调节肌肉发育分化的新路径,阐释哺乳动物生肌分子时间,寻找肌肉组织中与生长发育相关的新LncRNA分子,深入研究与生长发育密切相关的LncRNA分子及其靶基因的生物学功能,阐明 LncRNA 在肌肉生长发育的调控机制,是肌肉发育遗传育种的主要研究内容。本文就LncRNA在哺乳动物肌肉生长发育、细胞生长、分化、增殖中的作用进行综述。 相似文献
13.
对32只关中奶山羊进行超排处理,获得胚胎263枚,其中囊胚122枚。采用机械法、酶消化法和免疫外科法分离囊胚83枚,得到内细胞团(ICM)65个。将ICM培养于小鼠胎儿成纤维细胞饲养层上,研究含血清和无血清条件下ICM的增殖规律,并比较添加不同生长因子对ICM增殖的影响。结果表明,无血清培养时,ICM细胞增殖相对较慢,分化减少;添加LIF、bFGF、两种同时添加或均不添加对原代ESC样集落形成率的影响不显著(P>0.05),但添加10 ng/mL bFGF稍微有助于ICM增殖。山羊ICM适宜于无血清培养。 相似文献
14.
表皮生长因子(EGF)是一种重要的多肽类生长因子,它对卵母细胞的体外成熟和早期胚胎的发育具有明显的促进作用。大量研究表明:EGF能够以旁分泌(Paracrine)或自分泌(Autocrine)的形式作用于胚胎组织中的EGFR,刺激内细胞团(ICM)和滋养外胚层的增殖,从而调节早期胚胎的发育。 相似文献
15.
利用机械方法二等份分割小鼠的桑椹胚、早期囊胚和晚期囊胚,并在体外培养分割的半胚到晚期囊胚。将这些囊胚移植到假孕受体鼠子宫内以评价他们附植后发育的能力。在体外培养中发现,囊胚期分割的胚胎比桑椹胚期分割的胚胎有较高的成活率。通过附植前胚胎细胞数量分析得知,囊胚期半胚的细胞数量大约是对照组的一半,但内细胞团细胞与整个胚胎细胞的数量比不变。虽然从半胚发育到囊胚期的胚胎附植率仅略低于对照组,但半胚形成胎儿的能力却显著低于全胚。组织学分析表明,附植后的这种低成活率现象是由于缺乏卵柱发育造成的,而此卵柱则与半胚中的内细胞团的细胞数量减少有关。移植到第3天假孕受体鼠中的半胚,附植后的发育情况明显地比移植到第4天受体中的好。 相似文献
16.
温度调控对南岭莪术根茎开花与花芽分化的影响 总被引：3，自引：0，他引：3
【目的】研究在贮藏、催芽及水养阶段温度调控对南岭莪术根茎休眠、花芽分化、开花及品质的影响,为南岭莪术生产开发,尤其是作为年宵花卉早春促成栽培提供指导。【方法】 设置南岭莪术根茎贮藏、催芽阶段温度与时间的组合处理,测量品质指标,并对不同发育阶段花芽分化过程进行外观和解剖形态学观察。【结果】 15℃贮藏30 d是南岭莪术根茎完成休眠的最短时间,贮藏时间超过60 d,开花率略有下降;根茎贮藏处理后,再经25—30℃催芽10—30 d可诱导花芽分化,并极显著地缩短了根茎定植到开花和展叶的时间;尤其是15℃贮藏50 d再经过30℃催芽30 d的根茎开花率高达92%,且花期可控制在春节。芽体发育到阶段1的南岭莪术根茎常温水培不能开花,此时为花芽分化起始期;发育到阶段2和阶段3的根茎分别进入花序原基及苞叶原基分化期和花蕾原基分化期,常温水培开花率分别为50%和66%;阶段4的根茎进入花器官分化期,花芽分化不可逆转,在常温水养开花率为100%。【结论】南岭莪术根茎贮藏可缩短休眠时间,高温诱导花芽分化,30℃培养至第4阶段进行市场交易,可成为高品质早春开花的水培花卉。 相似文献
17.
Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control 总被引：13，自引：0，他引：13
C B Klein K Conway X W Wang R K Bhamra X H Lin M D Cohen L Annab J C Barrett M Costa 《Science (New York, N.Y.)》1991,251(4995):796-799
Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells. At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells. However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells. Full senescing activity of the intact hamster X chromosome was restored by treatment of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA. These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms. 相似文献
18.
近年来研究发现真核生物基因组中的许多重复序列以及基因的内含子参与基因表达的调控。在这些重复序列中,有一种广泛分布于基因组中的逆转座子LINE-1,目前发现其对细胞的增殖与分化以及肿瘤的发生起着非常重要的作用,具体表现为影响基因的转录及整个基因组的稳定性、参与X染色体失活及基因组进化等。在正常细胞的分化调控中,基因的激活与沉默具有时间与空间的特异性,实现其“预定”的、有序的、不可逆转的分化过程。主要阐述了逆转座子LINE-1的结构特征和其在基因组中的调控作用及这些作用影响基因表达从而调节生物体的生命活动。研究LINE-1的调控机制对认识细胞的时空调控以及癌症的发生与发展具有重要的价值。 相似文献
19.
Epigenetic reprogramming in mammalian development 总被引：1，自引：0，他引：1
DNA methylation is a major epigenetic modification of the genome that regulates crucial aspects of its function. Genomic methylation patterns in somatic differentiated cells are generally stable and heritable. However, in mammals there are at least two developmental periods-in germ cells and in preimplantation embryos-in which methylation patterns are reprogrammed genome wide, generating cells with a broad developmental potential. Epigenetic reprogramming in germ cells is critical for imprinting; reprogramming in early embryos also affects imprinting. Reprogramming is likely to have a crucial role in establishing nuclear totipotency in normal development and in cloned animals, and in the erasure of acquired epigenetic information. A role of reprogramming in stem cell differentiation is also envisaged. DNA methylation is one of the best-studied epigenetic modifications of DNA in all unicellular and multicellular organisms. In mammals and other vertebrates, methylation occurs predominantly at the symmetrical dinucleotide CpG (1-4). Symmetrical methylation and the discovery of a DNA methyltransferase that prefers a hemimethylated substrate, Dnmt1 (4), suggested a mechanism by which specific patterns of methylation in the genome could be maintained. Patterns imposed on the genome at defined developmental time points in precursor cells could be maintained by Dnmt1, and would lead to predetermined programs of gene expression during development in descendants of the precursor cells (5, 6). This provided a means to explain how patterns of differentiation could be maintained by populations of cells. In addition, specific demethylation events in differentiated tissues could then lead to further changes in gene expression as needed. Neat and convincing as this model is, it is still largely unsubstantiated. While effects of methylation on expression of specific genes, particularly imprinted ones (7) and some retrotransposons (8), have been demonstrated in vivo, it is still unclear whether or not methylation is involved in the control of gene expression during normal development (9-13). Although enzymes have been identified that can methylate DNA de novo (Dnmt3a and Dnmt3b) (14), it is unknown how specific patterns of methylation are established in the genome. Mechanisms for active demethylation have been suggested, but no enzymes have been identified that carry out this function in vivo (15-17). Genomewide alterations in methylation-brought about, for example, by knockouts of the methylase genes-result in embryo lethality or developmental defects, but the basis for abnormal development still remains to be discovered (7, 14). What is clear, however, is that in mammals there are developmental periods of genomewide reprogramming of methylation patterns in vivo. Typically, a substantial part of the genome is demethylated, and after some time remethylated, in a cell- or tissue-specific pattern. The developmental dynamics of these reprogramming events, as well as some of the enzymatic mechanisms involved and the biological purposes, are beginning to be understood. Here we look at what is known about reprogramming in mammals and discuss how it might relate to developmental potency and imprinting. 相似文献
20.
比较了牛胚胎与小鼠胚胎在体外培养过程中的生长行为，结果表明，牛滋养层细胞与内细胞团（ｉｎｎｅｒ ｃｅｌｌｍａｓｓ，简称ＩＣＭ）连接不紧密，其迅速增殖，形成半透明囊腔结构；小鼠胚胎滋养层与ＩＣＭ密切相连，形成盘状结构，并推移原代小鼠胎儿成纤维细胞（Ｐｒｉｍａｒｙ ｍｕｒｉｎｅ ｅｍｂｒｙｏｓｆｉｂｒｏｂｌａｓｔ，ＰＭＥＦ）饲养层。牛ＩＣＭ形态呈现多样性，表现为团状、条状、网状和混合型；小鼠ＩＣＭ形态单一，多呈圆盘状。体外培养的牛胚胎发育速度比小鼠胚胎迟缓，牛ＩＣＭ初次传代时间为胚胎体外培养开始后５～６ｄ，小鼠ＩＣＭ初次传代时间为胚胎体外培养后３～４ｄ。牛ＩＣＭ分化程度由小到大依次为团状ＩＣＭ、条状ＩＣＭ、混合型正 和网状ＩＣＭ。牛和小鼠胚胎附着率及ＩＣＭ克隆率由大到小均依次为孵化胚、囊胚和桑褡胚，但桑褡胚和囊胚附着率和ＩＣＭ克隆率均无显著差异（Ｐ＞０．０５）。与全胚相比较，牛和小鼠裸胚（无透明带或透明带不完整的胚胎）贴壁时间提前，但ＩＣＭ形成率和ＩＣＭ的生长行为均无显著差异；小鼠和牛桑椹胚卵裂球（中、晚期）体外分化抑制培养，形成亚囊胚而不能获得 ＥＳ细胞；剥离牛胚胎滋胚层细胞，ＩＣＭ细胞更易分化。 相似文献