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发育中的小鼠胎儿的时空DNA甲基组动态

Yupeng He^1,2, Manoj Hariharan¹, David U Gorkin³

¹Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.

|July 31, 2020

概括

这项研究绘制了小鼠发育过程中的DNA甲基化,揭示了对组织形成和基因调节至关重要的CG和非CG甲基化的动态变化. 这些发现提供了关于发育障碍的见解.

科学领域:

发育生物学
表观遗传学
基因组学

背景情况:

细胞酸DNA甲基化对于哺乳动物的发育至关重要,但其精确的时空分布尚未完全理解.
关于胚胎发育过程中的DNA甲基化模式的数据有限.

研究的目的:

在各种小鼠组织和发育阶段全面描述甲基瘤.
确定具有动态CG甲基化变异的基因组区域.
研究非CG甲基化在发育过程中的基因调节作用.

主要方法:

在9个发育阶段,从12个小鼠组织中分析168个甲基组.
甲基瘤的比较分析以确定CG甲基化的变化.
整合DNA甲基化,基因组修饰和染色质可访问性数据.

主要成果:

鉴定了1,808,810个具有CG甲基化变异的基因组区域.
在胎儿发育过程中主要的CG甲基化损失的观察,出生后逆转.
胎儿发育晚期基因中非CG甲基化的积累,与转录抑制相关.
预测了461,141种可谓的发育组织特异性增强剂.

结论:

时空表观基因组图为研究组织发育中的基因调节提供了宝贵的资源.
已识别的增强剂对与疾病相关的遗传变异进行了丰富,这表明它们在人类发育障碍中的作用.
这项工作为研究表观遗传对发育异常的贡献奠定了基础.

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相关概念视频

In-vitro Mutagenesis

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.