Dataset Information

Multiscale 3D Genome Rewiring during Mouse Neural Development.

ABSTRACT: Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo. Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.

SUBMITTER: Bonev B

PROVIDER: S-EPMC5651218 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Multiscale 3D Genome Rewiring during Mouse Neural Development.

Bonev Boyan B Mendelson Cohen Netta N Szabo Quentin Q Fritsch Lauriane L Papadopoulos Giorgio L GL Lubling Yaniv Y Xu Xiaole X Lv Xiaodan X Hugnot Jean-Philippe JP Tanay Amos A Cavalli Giacomo G

Cell 20171001 3

Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is ...[more]

PMID: 29053968

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Project description:Histone modification plays an important role in cell differentiation and tissue development. A recent study has shown that the dimethylation of lysine 4 residue on histone 3 (H3K4me2) marks the gene body area of tissue specific genes in the human CD4+ T cells and neural cells. However, little is known of the H3k4me2 distribution dynamics through the cell differentiation and tissue development.We applied several clustering methods including K-means, hierarchical and principle component analysis on H3K4me2 ChIP-seq data from embryonic stem cell, neural progenitor cell and whole brain of mouse, trying to identify genes with the H3K4me2 binding on the gene body region in different cell development stage and study their redistribution in different tissue development stages.A cluster of 356 genes with heavy H3K4me2 labeling in the gene body region was identified in the mouse whole brain tissue using K-means clustering. They are highly enriched with neural system related functions and pathways, and are involved in several central neural system diseases. The distribution of H3K4me2 on neural function related genes follows three distinctive patterns: a group of genes contain constant heavy H3K4me2 marks in the gene body from embryonic stem cell stage through neural progenitor stage to matured brain tissue stage; another group of gene have little H3K4me2 marks until cells mature into brain cells; the majority of the genes acquired H3K4me2 marks in the neural progenitor cell stage, and gain heavy labeling in the matured brain cell stage. Gene ontology enrichment analysis also revealed corresponding gene ontology terms that fit in the scenario of each cell developmental stages.We investigated the process of the H3K4me2 mark redistribution during tissue specificity development for mouse brain tissue. Our analysis confirmed the previous report that heavy labeling of H3K4me2 in the downstream of TSS marks tissue specific genes. These genes show remarkable enrichment in central neural system related diseases. Furthermore, we have shown that H3K4me2 labeling can be acquired as early as the embryonic stem cell stage, and its distribution is dynamic and progressive throughout cell differentiation and tissue development.

Dataset Information

Multiscale 3D Genome Rewiring during Mouse Neural Development.

Publications

Multiscale 3D Genome Rewiring during Mouse Neural Development.

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