小柯机器人

科学家绘制出发育过程中小鼠胚胎的时空DNA甲基化动态
2020-08-01 23:21

美国索尔克生物研究所Joseph R. Ecker小组绘制出发育过程中小鼠胚胎的时空DNA甲基化动态。相关论文于2020年7月29日发表在《自然》杂志上。

作为小鼠ENCODE(Encyclopedia of DNA Elements)项目的一部分,研究人员从胚胎发生到成年的9个发育阶段,对来自12个小鼠组织或器官的168个甲基化基因组进行了分析。通过比较不同发育阶段的不同组织或器官的甲基化组,研究人员确定了1,808,810个基因组区域,这些区域显示了CG甲基化差异。这些DNA元件在胎儿发育过程中显著丢失CG甲基化,而这种趋势在出生后就逆转了。

在胚胎发育的后期,非CG甲基化在关键的发育转录因子基因体内积累,这与其转录抑制相吻合。全基因组DNA甲基化、组蛋白修饰和染色质可及性数据的整合使研究人员能够预测461,141个假定的发育组织特异性增强子,并且其人类直系同源物丰富了与疾病相关的遗传变异。这些时空表观基因组图谱为研究组织或器官发育过程中的基因调控提供了资源,也是研究与人类发育障碍相关调控元件的起点。

据悉,胞嘧啶DNA甲基化对于哺乳动物的发育至关重要,但对于其在发育中的胚胎的时空分布的了解仍然有限。

附:英文原文

Title: Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Author: Yupeng He, Manoj Hariharan, David U. Gorkin, Diane E. Dickel, Chongyuan Luo, Rosa G. Castanon, Joseph R. Nery, Ah Young Lee, Yuan Zhao, Hui Huang, Brian A. Williams, Diane Trout, Henry Amrhein, Rongxin Fang, Huaming Chen, Bin Li, Axel Visel, Len A. Pennacchio, Bing Ren, Joseph R. Ecker

Issue&Volume: 2020-07-29

Abstract: Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited1,2. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders.

DOI: 10.1038/s41586-020-2119-x

Source: https://www.nature.com/articles/s41586-020-2119-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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