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1.
Epigenetic reprogramming in mammalian development   总被引:1,自引:0,他引:1  
Reik W  Dean W  Walter J 《Science (New York, N.Y.)》2001,293(5532):1089-1093
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   

2.
Epigenetic decisions in mammalian germ cells   总被引:1,自引:0,他引:1  
  相似文献   

3.
Plants and filamentous fungi share with mammals enzymes responsible for DNA methylation. In these organisms, DNA methylation is associated with gene silencing and transposon control. However, plants and fungi differ from mammals in the genomic distribution, sequence specificity, and heritability of methylation. We consider the role that transposons play in establishing methylation patterns and the epigenetic consequences of their perturbation.  相似文献   

4.
表观遗传学是研究基因核苷酸序列不发生改变的情况下,基因表达的可遗传的变化的一门遗传学分支学科。表观遗传的现象较多,已有DNA甲基化、组蛋白修饰、染色质重塑、非编码RNA调控、基因组印记、基因沉默、母体效应、核仁显性、休眠转座子激活等。在集约化的水产养殖模式中,养殖密度提高,投喂过量等均会产生刺激鱼类生长的环境因素。已有文献报道,环境胁迫因素刺激可影响鱼类表观遗传修饰,但并未涉及遗传信息的变化,所以在一定范围内可以解释为表型变化。本研究围绕环境胁迫因素对鱼类表观遗传产生的影响进行了综述,为进一步阐释环境因素与基因互作关系提供了参考。  相似文献   

5.
【目的】分析LEF1基因在红棕色与青灰色巴什拜羊皮肤组织中DNA甲基化与mRNA的表达水平。【方法】运用BSP(亚硫酸盐修饰后测序PCR)与RT-RCR(实时荧光定量PCR),检测不同毛色巴什拜羊皮肤组织LEF1基因启动子区的甲基化水平与mRNA表达量。【结果】在红棕色巴什拜羊皮肤组织中的LEF1基因启动子区的甲基化水平高于青灰色的甲基化水平,且二者甲基化CpG位点不同,二者呈显著的负相关(P< 0.05)。【结论】DNA甲基化水平对红棕色与青灰色巴什拜羊的毛色形成具有调节作用,可作为一个候选的巴什拜羊毛色遗传标记。  相似文献   

6.
籼稻精米重量性状的发育遗传分析   总被引:5,自引:0,他引:5  
采用包括胚乳、细胞质和母体植株等不同遗传体系基因效应的数量性状发育遗传模型和统计分析方法,分析了籼稻4个发育时期的精米重量性状.结果表明三倍体胚乳和二倍体母株基因的加性效应和显性效应以及细胞质效应可以明显影响各个稻米发育时期的精米重量,但主要为二倍体母株的核基因效应,其次为三倍体胚乳核基因效应.基因加性效应在稻米4个发育时期的精米重量表现中起着主要作用,选择可以取得良好的改良效果.条件方差分量分析结果表明,胚乳、细胞质和母体植株中控制精米重量性状表现的基因在多数稻米发育时期均有新的表达,且以稻米发育前期为主,其中开花后第8~14日是控制精米重量性状表现的基因表达最为活跃的时期,各遗传体系在接近稻米成熟时(开花后第22~28日)的新基因表达量尤其是基因的加性效应会明显下降,一些基因效应尤其是净细胞质效应存在着个别发育时期间断表达的现象.稻米不同发育时期的条件和非条件遗传效应预测值表明,作5等亲本可以明显提高后代的精米重量.  相似文献   

7.
The inheritance of epigenetic defects   总被引:58,自引:0,他引:58  
Evidence from many sources shows that the control of gene expression in higher organisms is related to the methylation of cytosine in DNA, and that the pattern of methylation is inherited. Loss of methylation, which can result from DNA damage, will lead to heritable abnormalities in gene expression, and these may be important in oncogenesis and aging. Transformed permanent lines often lose gene activity through de novo methylation. It is proposed that epigenetic defects in germline cells due to loss of methylation can be repaired by recombination at meiosis but that some are transmitted to offspring.  相似文献   

8.
9.
谷类作物胚乳品质性状的遗传研究   总被引:44,自引:2,他引:42  
本文综述谷类作物胚乳品质性状遗传研究的最新进展。主要包括:⑴胚乳性状的遗传特征,⑵胚乳性状的遗传控制,⑶胚乳性状的三倍体遗传模型,⑷胚乳性状的质量-数量遗传分析。胚乳性状的遗传表达,可能受胚乳基因型或/和母株基因型控制,还可能存在细胞质效应,鉴别遗传控制是胚乳性状遗传研究的基础。由胚乳基因型控制的性状,应用三倍体的遗传模型描述。既有主基因又有微基因遗传效应的胚乳性状需用质量 - 数量的遗传分析方法。  相似文献   

10.
11.
采用RT–PCR技术扩增和克隆鸭Myo G基因启动子,并对其启动子序列进行生物信息学分析,采用Sequenom Mass Array技术检测Cp G岛在鸭肌肉组织中的甲基化水平,用q RT–PCR检测Myo G基因的表达量。结果表明,扩增得到鸭Myo G基因启动子序列2 730 bp,对启动子序列预测后,发现存在2个Cp G岛,其中Cp G岛(–2 536~–1 997 bp)存在5个转录因子结合位点和多个真核生物结构元件。甲基化检测结果表明:在鸭的个体和组织水平上,启动子甲基化率均未聚类在一起;Cp G位点甲基化频率存在个体差异,22%Cp G位点的甲基化频率与Myo G的m RNA表达量呈负相关(P0.05),78%Cp G位点的甲基化频率呈正相关(P0.05),其中,腿肌甲基化位点Cp G_1、Cp G_26.27.28.29的甲基化频率与Myo G基因表达水平均呈显著相关(P0.05)。Myo G基因在鸭与在哺乳动物中的转录调控机制存在差异。试验中发现多个影响鸭Myo G基因转录的潜在甲基化位点,其中Cp G_1与Cp G_26.27.28.29能通过DNA甲基化修饰影响Myo G基因在鸭腿肌中的转录。本研究结果可为鸭Myo G基因转录调控提供参考依据。  相似文献   

12.
Genomic imprinting causes parental origin-specific monoallelic gene expression through differential DNA methylation established in the parental germ line. However, the mechanisms underlying how specific sequences are selectively methylated are not fully understood. We have found that the components of the PIWI-interacting RNA (piRNA) pathway are required for de novo methylation of the differentially methylated region (DMR) of the imprinted mouse Rasgrf1 locus, but not other paternally imprinted loci. A retrotransposon sequence within a noncoding RNA spanning the DMR was targeted by piRNAs generated from a different locus. A direct repeat in the DMR, which is required for the methylation and imprinting of Rasgrf1, served as a promoter for this RNA. We propose a model in which piRNAs and a target RNA direct the sequence-specific methylation of Rasgrf1.  相似文献   

13.
孟凡荣  司志飞  刘昊英 《安徽农业科学》2007,35(36):11757-11757,11759
DNA甲基化是生物体内普遍存在的一种基因修饰现象,在生物体内发挥着重要的生物学功能。大量研究表明,DNA甲基化不仅可以遗传,而且存在特定的动态变化模式。综述了植物DNA甲基化的特点、模式以及它们与植物生长、发育和基因表达调控的关系。  相似文献   

14.
15.
Based on dynamic analysis for the Front Wheel Assist(FWA) tractor,a calculating and analysing method on selecting the optimum coefficient of inharmonious motion for the FWA tractor is described in this paper and the mathematical odels are also established.The article first time dlefines the ratio of thrust of front wheels to that of rear wheels.Which is an important parameter affeeting the tractive performance of the FWA tractor and establishes the conditon of no power circulation of the FWA tractor.The optimum coefficient of inharmonious motion for a FWA tractor (UTB-445)is also given.  相似文献   

16.
UHRF1 plays a role in maintaining DNA methylation in mammalian cells   总被引:1,自引:0,他引:1  
Epigenetic inheritance in mammals relies in part on robust propagation of DNA methylation patterns throughout development. We show that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation. UHRF1 colocalizes with the maintenance DNA methyltransferase protein DNMT1 throughout S phase. UHRF1 appears to tether DNMT1 to chromatin through its direct interaction with DNMT1. Furthermore UHRF1 contains a methyl DNA binding domain, the SRA (SET and RING associated) domain, that shows strong preferential binding to hemimethylated CG sites, the physiological substrate for DNMT1. These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation.  相似文献   

17.
The Arabidopsis gene DDM1 is required to maintain DNA methylation levels and is responsible for transposon and transgene silencing. However, rather than encoding a DNA methyltransferase, DDM1 has similarity to the SWI/SNF family of adenosine triphosphate-dependent chromatin remodeling genes, suggesting an indirect role in DNA methylation. Here we show that DDM1 is also required to maintain histone H3 methylation patterns. In wild-type heterochromatin, transposons and silent genes are associated with histone H3 methylated at lysine 9, whereas known genes are preferentially associated with methylated lysine 4. In ddm1 heterochromatin, DNA methylation is lost, and methylation of lysine 9 is largely replaced by methylation of lysine 4. Because DNA methylation has recently been shown to depend on histone H3 lysine 9 methylation, our results suggest that transposon methylation may be guided by histone H3 methylation in plant genomes. This would account for the epigenetic inheritance of hypomethylated DNA once histone H3 methylation patterns are altered.  相似文献   

18.
二氧化硫胁迫诱导拟南芥NIT2基因DNA甲基化修饰   总被引:1,自引:1,他引:0  
DNA甲基化是一种重要的表观遗传修饰形式。利用亚硫酸氢盐修饰后测序法和甲基化敏感性限制性内切酶-PCR(MSRE-PCR)法,研究SO2胁迫对拟南芥腈水解酶(NIT2)基因序列中胞嘧啶甲基化状态的影响,分析甲基化特征改变在植物胁迫应答过程中的作用。研究发现,30 mg.m-3的SO2连续熏气3 d后,拟南芥植株地上组织细胞中NIT2基因启动子区域CG和CHH(H为C,A或T)位点甲基化水平下降,总甲基化水平降低,但未检出编码区5′端目的片段中CCGG位点甲基化状态的改变。RT-PCR分析表明,SO2胁迫组拟南芥植株地上组织细胞中NIT2基因的转录水平高于对照组。研究结果表明,SO2胁迫导致拟南芥NIT2基因启动子区甲基化水平降低,NIT2基因转录上调,说明SO2胁迫能诱发拟南芥基因胞嘧啶甲基化水平改变,启动子区甲基化水平的降低可能与防御基因的诱导表达有关,胞嘧啶甲基化修饰参与了植物的抗逆生理过程。  相似文献   

19.
DNA甲基化及其生物学功能   总被引:4,自引:0,他引:4  
DNA甲基化是真核细胞基因组重要修饰方式之一。机体有建立和维持DNA甲基化的机制。DNA甲基化通过与反式因子相互作用或通过改变染色体结构而影响基因的表达,在胚胎发育、X染色体失活、基因组印记等方面起着重要作用。DNA甲基化为哺乳动物的发育、遗传性疾病和肿瘤的发生、生物进化、性状的遗传控制等的研究提供了新的途径。  相似文献   

20.
BPA不影响卵母细胞减数分裂相关基因Dazl的甲基化   总被引:1,自引:0,他引:1  
为了探讨环境雌激素BPA对小鼠卵母细胞减数分裂相关基因Dazl甲基化的影响,本研究通过给孕鼠饮用含有BPA的水方式使胎鼠在发育过程中接触BPA,利用重亚硫酸盐测序法,分析了胎鼠生殖嵴卵母细胞不同发育时期Dazl甲基化水平的变化。结果显示:Dazl在减数分裂期间处于低甲基化水平,无论对照组或处理组均低于10%,说明Dazl的低甲基化对维持减数分裂的正常进行有重要作用;对照组与处理组的甲基化水平相当,差异不显著,说明本研究的BPA浓度不影响卵母细胞Dazl的甲基化水平。  相似文献   

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