Suppr超能文献

DNA去甲基化酶和组蛋白去甲基酶在牛胚胎中的时空表达

Spatiotemporal expression of DNA demethylation enzymes and histone demethylases in bovine embryos.

作者信息

Pagé-Larivière Florence, Sirard Marc-André

机构信息

Centre de Recherche en Biologie de la Reproduction, Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Université Laval , Québec, QC, Canada, G1V 0A6 .

出版信息

Cell Reprogram. 2014 Feb;16(1):40-53. doi: 10.1089/cell.2013.0055.

Abstract

Fertilization in bovines causes profound changes in the epigenetic profile that affect both DNA methylation patterns and posttranslational histone modifications. These dynamic changes have a great potential for activating pluripotency genes and unfolding certain chromatin regions to recruit different transcription factors. Surprisingly, while the fundamental function of epigenetic remodeling is well understood, the bases of the process are still unknown. Recent developments in epigenetics suggest a multistep demethylation process that would imply the prior modification of the methylated cytosine or methyl group, followed by a DNA repair mechanism implicating enzymes such as activation-induced cytidine deaminase (AICDA) and ten-eleven translocation (TET) dioxygenase. Their functions seem to differ from one species to the other, and they are not yet well characterized in large mammals. Histones have, for their part, many associated and specific lysine demethylases (KDM). Their expression profile in large mammals is not well characterized. We have been interested in characterizing the spatiotemporal expression profile for each of the genes studied to increase our understanding of the molecular interactions following fertilization in early bovine embryo stages. Bovine oocytes and embryos at various preimplantation stages were collected following in vitro fertilization protocol. Total RNA for AICDA, TET1, TET2, TET3, KDM3A, KDM4A, KDM4C, and KDM5B was extracted, reverse transcribed into cDNA, and amplified by real-time PCR. Other embryo pools were collected, and protein localization of the genes studied was characterized. TET3 dioxygenase was present in the very first embryo stages, in contrast to TET1 and AICDA. Histone demethylases KDM3A, KDM4A, and KDM4C were expressed before and after embryonic genome activation, whereas KDM5B was mainly expressed during the blastocyst period. DNA demethylation following fertilization in bovines is not accomplished by AICDA but most probably by TET3. Histone demethylation is carried out by, among others, KDM3A, KDM4A, and KDM4C, which could act in sequence to demethylate histones prior to DNA demethylation of the female chromosomes.

摘要

牛的受精过程会导致表观遗传特征发生深刻变化,这会影响DNA甲基化模式和翻译后组蛋白修饰。这些动态变化在激活多能性基因以及展开某些染色质区域以招募不同转录因子方面具有巨大潜力。令人惊讶的是,虽然表观遗传重塑的基本功能已为人所熟知,但其过程的基础仍然未知。表观遗传学的最新进展表明存在一个多步骤的去甲基化过程,这意味着甲基化胞嘧啶或甲基基团会先发生修饰,随后是涉及诸如激活诱导胞苷脱氨酶(AICDA)和十一-易位(TET)双加氧酶等酶的DNA修复机制。它们的功能似乎因物种而异,并且在大型哺乳动物中尚未得到很好的表征。就组蛋白而言,有许多相关的特异性赖氨酸去甲基化酶(KDM)。它们在大型哺乳动物中的表达谱尚未得到很好的表征。我们一直致力于表征所研究的每个基因的时空表达谱,以增进我们对牛早期胚胎阶段受精后分子相互作用的理解。按照体外受精方案收集处于各种植入前阶段的牛卵母细胞和胚胎。提取AICDA、TET1、TET2、TET3、KDM3A、KDM4A、KDM4C和KDM5B的总RNA,逆转录成cDNA,并通过实时PCR进行扩增。收集其他胚胎样本,并对所研究基因的蛋白质定位进行表征。与TET1和AICDA不同,TET3双加氧酶在最初的胚胎阶段就已存在。组蛋白去甲基化酶KDM3A、KDM4A和KDM4C在胚胎基因组激活前后均有表达,而KDM5B主要在囊胚期表达。牛受精后的DNA去甲基化不是由AICDA完成的,很可能是由TET3完成的。组蛋白去甲基化由KDM3A、KDM4A和KDM4C等完成,它们可能在雌性染色体DNA去甲基化之前依次作用于组蛋白去甲基化。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验