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早期胚胎谱系特化过程中的表观遗传重排。

Epigenetic reorganization during early embryonic lineage specification.

作者信息

Fang Haitong, Luo Zhuojuan, Lin Chengqi

机构信息

School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China.

Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.

出版信息

Genes Genomics. 2022 Mar;44(3):379-387. doi: 10.1007/s13258-021-01213-w. Epub 2022 Feb 8.

Abstract

BACKGROUND

Dynamic chromatin reorganization occurs during two waves of cell lineage specification process, blastocyst formation and gastrulation, to generate distinct cell types. Epigenetic defects have been associated with severe developmental defects and diseases. How epigenetic remodeling coordinates the two lineage specification waves is becoming uncovered, benefiting from the development and application of new technologies including low-input or single-cell epigenome analysis approached in the past few years.

OBJECTIVE

In this review, we aim to highlight the most recent findings on epigenetic remodeling in cell lineage specification during blastocyst formation and gastrulation.

METHODS

First, we introduce how DNA methylation dynamically changes in blastocyst formation and gastrulation and its function in transcriptional regulation lineage-specific genes. Then, we discuss widespread remodeling of histone modification at promoters and enhancers in orchestrating the trajectory of cell lineage specification. Finally, we review dynamics of chromatin accessibility and 3D structure regulating developmental gene expression and associating with specific transcription factor binding events at stage specific manner. We also highlight the key questions that remain to be answered to fully understand chromatin regulation and reorganization in lineage specification.

CONCLUSION

Here, we summarize the recent advances and discoveries on epigenetic reorganization and its roles in blastocyst formation and gastrulation, and how it cooperates with the lineage specification, painting from global sequencing data from mouse in vivo tissues.

摘要

背景

动态染色质重组发生在细胞谱系特化过程的两个阶段,即囊胚形成和原肠胚形成,以产生不同的细胞类型。表观遗传缺陷与严重的发育缺陷和疾病有关。得益于包括过去几年出现的低输入或单细胞表观基因组分析方法在内的新技术的发展和应用,表观遗传重塑如何协调这两个谱系特化阶段正逐渐被揭示。

目的

在本综述中,我们旨在强调囊胚形成和原肠胚形成过程中细胞谱系特化过程中表观遗传重塑的最新发现。

方法

首先,我们介绍DNA甲基化在囊胚形成和原肠胚形成过程中如何动态变化及其在转录调控谱系特异性基因中的作用。然后,我们讨论启动子和增强子处组蛋白修饰的广泛重塑在编排细胞谱系特化轨迹中的作用。最后,我们回顾染色质可及性和三维结构的动态变化,其如何调节发育基因表达并以阶段特异性方式与特定转录因子结合事件相关联。我们还强调了在充分理解谱系特化过程中的染色质调控和重组方面仍有待回答的关键问题。

结论

在此,我们总结了表观遗传重组及其在囊胚形成和原肠胚形成中的作用的最新进展和发现,以及它如何与谱系特化协同作用,并借鉴了来自小鼠体内组织的全基因组测序数据。

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