动态染色质重组发生在两波细胞谱系规范过程中,囊胚形成和原肠胚形成,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。表观遗传重塑如何协调两个谱系规范波正在被发现,受益于过去几年中采用的包括低投入或单细胞表观基因组分析在内的新技术的开发和应用。
在这篇评论中,我们旨在强调在囊胚形成和原肠胚形成过程中细胞谱系规范中表观遗传重塑的最新发现。
首先,我们介绍了DNA甲基化在胚泡形成和原肠胚形成中的动态变化及其在转录调控谱系特异性基因中的功能。然后,我们讨论了在启动子和增强子上组蛋白修饰的广泛重塑,以协调细胞谱系规范的轨迹。最后,我们回顾了染色质可及性和3D结构调节发育基因表达的动力学,并以阶段特异性方式与特定转录因子结合事件相关联。我们还强调了有待回答的关键问题,以充分理解谱系规范中的染色质调节和重组。
这里,我们总结了表观遗传重组及其在胚泡形成和原肠胚形成中的作用的最新进展和发现,以及它如何与谱系规范合作,从小鼠体内组织的全局测序数据绘制。
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.
In this review, we aim to highlight the most recent findings on epigenetic remodeling in cell lineage specification during blastocyst formation and gastrulation.
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.
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.