Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development
| Autor: | Jinsong Li, Yu Hou, He Xu, Boqiang Hu, Su Feng, Yun Qian, Xianfa Yang, Yunbo Qiao, Jiaoyang Liao, Ran Wang, Ji Dong, Fang Yu, Guangdun Peng, Fuchou Tang, Yingying Chen, Naihe Jing |
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| Rok vydání: | 2019 |
| Předmět: |
Neurogenesis
Mice Transgenic Ectoderm Germ layer Cell fate determination Biology Article Epigenesis Genetic Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Enhancer Molecular Biology Cells Cultured Embryonic Stem Cells 030304 developmental biology Epigenomics Regulation of gene expression 0303 health sciences Gastrulation Brain Gene Expression Regulation Developmental Gastrula Cell Biology Epigenome Embryo Mammalian Cell biology Mice Inbred C57BL Enhancer Elements Genetic medicine.anatomical_structure Female Transcriptome Germ Layers 030217 neurology & neurosurgery |
| Zdroj: | Cell Res |
| ISSN: | 1748-7838 1001-0602 |
| DOI: | 10.1038/s41422-019-0234-8 |
| Popis: | Primary germ layers have the potential to form all tissues in the mature organism, and their formation during gastrulation requires precise epigenetic modulation of both proximal and distal regulatory elements. Previous studies indicated that spatial and temporal patterns of gene expression in the gastrula predispose individual regions to distinct cell fates. However, the underlying epigenetic mechanisms remain largely unexplored. Here, we profile the spatiotemporal landscape of the epigenome and transcriptome of the mouse gastrula. We reveal the asynchronous dynamics of proximal chromatin states during germ layer formation as well as unique gastrula-specific epigenomic features of regulatory elements, which have strong usage turnover dynamics and clear germ layer-specific signatures. Importantly, we also find that enhancers around organogenetic genes, which are weakly expressed at the gastrulation stage, are frequently pre-marked by histone H3 lysine 27 acetylation (H3K27ac) in the gastrula. By using the transgenic mice and genome editing system, we demonstrate that a pre-marked enhancer, which is located in the intron of a brain-specific gene 2510009E07Rik, exhibits specific enhancer activity in the ectoderm and future brain tissue, and also executes important function during mouse neural differentiation. Taken together, our study provides the comprehensive epigenetic information for embryonic patterning during mouse gastrulation, demonstrates the importance of gastrula pre-marked enhancers in regulating the correct development of the mouse embryo, and thus broadens the current understanding of mammalian embryonic development and related diseases. |
| Databáze: | OpenAIRE |
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