哺乳动物早期胚胎的剂量补偿作用及其对发育的影响

剂量补偿是使X连锁基因的表达水平在两性间达到平衡的过程。哺乳动物是通过随机失活雌性的一条X染色体实现剂量补偿。X染色体失活开始于X染色体失活中心（XIC）,然后传播到整条染色体。Xist基因定位于XIC中,参与X染色体失活的启动。本文主要通过分析雄核生殖胚胎、雌核生殖胚胎和正常胚胎发育中X连锁基因表达,概括了X染色体失活（XCI）在哺乳动物早期胚胎发育中作用,综述了哺乳动物早期胚胎的剂量补偿作用及其对发育的影响。     

X染色体失活、失活逃逸及相关疾病的研究进展

剂量补偿效应是表观遗传的机制之一,它是指使X连锁基因的表达水平在两性间达到平衡的过程。不同的物种所实现剂量补偿的机制不同,人同其他哺乳动物的剂量补偿机制是雌性个体随即失活一条X染色体。但最近的研究发现,在人和小鼠的失活X染色体上有些基因仍能表达,逃避了失活。目前,许多人类疾病尤其是具有女性发病优势病症的发生与治疗可能与这些逃逸基因密切相关。针对以上内容的最新进展作了相关综述。     

非编码RNA在胚胎发育过程中的作用

胚胎发育是一个复杂的过程,其发生受到了很多转录调控因子的调控。随着高通量深度测序技术的发展,研究发现非编码RNA(ncRNA)对动物胚胎发育、X染色体失活、性别调控、脑部发育都具有十分重要的调控作用。其中,miRNA主要通过与其靶向mRNA的3′UTR结合参与调控胚胎发育的相关基因;lncRNA通过转录干扰或是修饰染色质来调控相关基因从而介导哺乳动物X染色体失活和昆虫W染色体的剂量补偿;piRNA通过沉默转座子来维持生殖细胞DNA完整性,并参与生殖细胞形成及家蚕性别调控;circRNA可以作为miRNA的海绵调控动物脑部的发育。本文拟从miRNA、lncRNA、piRNA、circRNA等ncRNA角度阐述其在胚胎发育过程中的研究进展,为进一步研究ncRNA参与调控动物胚胎发育过程的作用机制提供参考。     

早期胚胎DNA甲基化研究进展

DNA甲基化修饰是研究最多的表观遗传修饰之一,在调控基因转录、染色体结构稳定、基因印迹、X染色体失活等方面发挥作用。尽管DNA甲基化是一种稳定的修饰,但其在个体发育进程中是动态变化的。目前,人们对早期胚胎发育中DNA甲基化修饰研究还不全面,随着全基因组DNA甲基化分析技术的进步,其在早期胚胎中的功能也逐渐揭示。作者主要论述了DNA甲基转移酶(DNMTs)的发现及其调控作用和DNA甲基化在早期胚胎中的作用。     

哺乳动物X染色体失活逃逸研究进展

雌性哺乳动物的失活X染色体上,大多数基因是转录沉默的。但是有些基因发生失活逃逸,在失活X染色体和正常X染色体上均表达。这些失活逃逸基因是引起性别二态性和雌性个体的表型变异性的潜在原因。文章主要综述了哺乳动物X染色体失活逃逸的分子机制研究新进展。     

哺乳动物X染色体失活机制及其应用

1X染色体失活的起源及发展 哺乳动物X染色体失活是指雌性动物为了平衡与雄性动物X染色体基因表达量的差异,而失活其中1条X染色体的现象。X和Y染色体起源于1对同源的常染色体,自然选择的压力导致了1条染色体的某个基因突变,从而产生了决定性别的基因,进而产生了性别分化。     

早期胚胎DNA甲基化研究进展

DNA甲基化修饰是研究最多的表观遗传修饰之一，在调控基因转录、染色体结构稳定、基因印迹、X染色体失活等方面发挥作用。尽管DNA甲基化是一种稳定的修饰，但其在个体发育进程中是动态变化的。目前，人们对早期胚胎发育中DNA甲基化修饰研究还不全面，随着全基因组DNA甲基化分析技术的进步，其在早期胚胎中的功能也逐渐揭示。作者主要论述了DNA甲基转移酶（DNMTs）的发现及其调控作用和DNA甲基化在早期胚胎中的作用。     

DNA甲基化在哺乳动物卵母细胞和早期胚胎发育中的研究进展

DNA甲基化(DNA methylation)是一种动态、可逆并可以遗传的表观遗传修饰模式,主要发生在哺乳动物原始生殖细胞和早期胚胎发育过程中,能够通过高动态和协同的核酶网络附着在DNA的CpG区域,同时还通过改变调控区域的功能状态进而调控基因表达且不影响DNA序列所携带的遗传信息。DNA甲基化主要涉及基因组印迹、转座元件沉默、X染色体失活和衰老等多种关键生理过程,在哺乳动物卵母细胞和胚胎发育中发挥着重要作用。本文介绍了DNA甲基化的建立与去除机制及其生物学功能,重点阐述了DNA甲基化在哺乳动物卵母细胞和胚胎发育过程中精准生成、维持、读取和删除等动态变化过程,为进一步研究哺乳动物表观遗传调控提供参考依据。     

测定卵裂球X染色体连锁基因剂量鉴别小鼠胚胎性别

将8-细胞小鼠胚胎除丢透明带,从中取出一个卵裂球,然后测定其与X染色体连锁的次黄嘌呤磷酸核糖基转移酶(Hypoxanthinephosphoribosyl transferase,HPRT)和与常染色体连锁的腺嘌呤磷酸核糖基转移酶(Adenine phosphoribosyl transferase,APRT)的活性,由于在8-细胞阶段,雌性胚胎中的两条X染色体均有活性,因此,可根据HPRT活性在基因剂量上的二倍差异,得到HPRT与APRT比率的双态分布图,而鉴别出雄性和雌性胚胎(?)将几批用这种方法鉴别了性别的胚胎移植到假孕受体小鼠子宫内。结果,其中八分之七胚胎的发育与对照组去了透明带的完整胚胎的发育相一致。通过测是X连锁基因剂量鉴别胚胎性别不仅准确,而且快速,要鉴别性别的胚胎移植前不需低温保存等待鉴别结果。     

哺乳动物DNA甲基化研究进展

在真核生物基因组中DNA甲基化是一种重要的修饰方式,也是一种重要的表观遗传学机制。通常甲基化发生在胞嘧啶第5个碳原子上,由DNA甲基化转移酶(DNMTs)家族催化形成的。DNA甲基化是一种可逆的过程,并且直接影响到基因的活性。DNA甲基化对于哺乳动物的正常发育起着非常重要的作用,并在很大程度上影响着哺乳动物重要的生物学进程,主要包括转录成分的沉默、基因失活、染色体的完整性和大部分基因的转录调控作用。     

Disease-dependent differently methylated regions (D-DMRs) of DNA are enriched on the X chromosome in uterine leiomyoma

Uterine leiomyoma is the most common benign tumor in women. Although responsible gene mutations have not been found in leiomyomas, they represent a progressive disease with irreversible symptoms. To characterize epigenetic features of uterine leiomyomas, the DNA methylation status of a paired sample of leiomyoma and normal myometrium was subjected to a microarray-based DNA methylation analysis with restriction tag-mediated amplification (D-REAM). In the leiomyoma, we identified an aberrant DNA methylation status for 463 hypomethylated and 318 hypermethylated genes. Although these changes occurred on all chromosomes, aberrantly hypomethylated genes were preferentially located on the X chromosome. Using paired samples of normal myometrium and leiomyoma from 6 hysterectomy patients, methylation-sensitive quantitative real-time PCR revealed 14 shared X chromosome genes with an abnormal DNA hypomethylation status (FAM9A, CPXCR1, CXORF45, TAF1, NXF5, VBP1, GABRE, DDX53, FHL1, BRCC3, DMD, GJB1, AP1S2 and PCDH11X) and one hypermethylated locus (HDAC8). Expression of XIST, which is involved in X chromosome inactivation, was equivalent in the normal myometrium and leiomyoma, indicating that the epigenetic abnormality on the X chromosome did not result from aberration of XIST gene expression. Based on these data, a unique epigenetic signature for uterine leiomyomas has emerged. The 14 hypomethylated and one hypermethylated loci provide valuable biomarkers for understanding the molecular pathogenesis of leiomyoma.     

胰岛素样生长因子2研究进展

胰岛素样生长因子2（IGF2）是迄今所知功能最复杂的生长调控因子,它能促进细胞的有丝分裂和分化,参与生后基因组重建,与X染色体的失活有重要关系。所有的这些功能说明IGF2在机体生长发育过程中的重要性。此外,IGF2与个体生长速度、瘦肉率、背膘厚等生产性能关系密切,在某些物种已经被作为候选基因确定下来。作为重要的印记基因,IGF2的表达状况与肿瘤,以及潜在肿瘤的发生发展关系密切,在肿瘤治疗方面起重要作用。文章综述了IGF2的基因结构、生物学作用、基因印记、生长发育和肿瘤的关系等方面的研究进展。     

DNA甲基化及其生物学功能

DNA甲基化是一种主要的表观遗传修饰,是调节基因表达的重要手段。作者在介绍了DNA甲基化机制、DNA甲基化的模式、DNA甲基化特点的基础上,重点论述了DNA甲基化发育分化、X染色体失活、基因组印记和杂种优势等方面的作用。     

哺乳动物Y染色体的测序进展

哺乳动物的性染色体由一对常染色体演化而来,其中X染色体在物种间相对保守,而Y染色体则存在很大的变异,包括染色体的大小、结构和基因数量等.研究Y染色体的遗传结构与变异,对于理解哺乳动物的起源进化、性别决定以及动物繁殖都具有重要意义.因此,文章综述了哺乳动物Y染色体的结构与变异,以及Sanger测序技术、二代测序技术、三代...     

Mapping genomic regions for reproductive traits in beef cattle: Inclusion of the X chromosome

Although the second largest chromosome of the genome, the X chromosome is usually excluded from genome-wide association studies (GWAS). Considering the presence and importance of genes on this chromosome that are involved in reproduction, the aim of this study was to evaluate the effect of its inclusion in GWAS on reproductive traits (scrotal circumference [SC], early pregnancy [P16] and age at first calving [AFC]) in a Nelore herd. Genotype data from 3,263 animals with the above-mentioned phenotypes were used. The results showed an increase in the variances explained by the autosomal markers for all traits when the X chromosome was not included. For SC, there was an increase of more than 10% for the windows on chromosomes 2 and 6. For P16, the effect was increased by almost 20% for windows on chromosome 5. The same pattern was found for AFC, with an increase of more than 10% for the most important windows. The results indicate that the noninclusion of the X chromosome can overestimate the effects of autosomes on SC, P16 and AFC not only because of the additive effect of the X chromosome itself but also because of its epistatic effect on autosomal genes.     

Identification of sex-specific polymorphic sequences in the goat amelogenin gene for embryo sexing

Amelogenin (AMEL) is a conserved gene located on the sex chromosomes of mammals. It is involved in the formation of enamel, which is the hard, white material that forms the protective outer layer of each tooth. In this study, we first cloned and determined the intron sequences of the goat AMELX and AMELY genes from female and male ear tissues. The polymorphic AMEL alleles were further analyzed by PCR-based RFLP and Southern blot hybridization analyses. Results showed that intron 5 nucleotide sequences of the goat AMELY gene contains multiple deletions/insertions and shares only 48.5% identity to intron 5 of the goat AMELX gene. Based on the polymorphic AMEL intron sequences, a set of sex-specific triplex primers was designed to PCR amplify a single fragment of 264 bp from the X chromosome of female goats and 2 fragments of 264 and 206 bp from the X and Y chromosomes, respectively, of male goats. An increased sensitivity for sex determination was reached with a single blastomere at the blastula stage isolated from goat embryos. A total of 43 goat embryos were used to estimate a 100% accuracy rate of this method confirmed by chromosomal karyotyping and live births. The embryo sexing technique has been successfully applied in different strains of goats including Alpine, Saanen, Nubian, and Taiwan goats.