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A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

ABSTRACT: A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

PROVIDER: PRJNA299708 | ENA |

REPOSITORIES: ENA

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A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.

Project description:We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs "facing" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.

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A three-dimensional map of the human genome at kilobase resolution reveals prinicples of chromatin looping

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Project description:The landscape of human epigenome undergoes extensive changes during development, leading to distinct transcription programs in different cell types. It is however still not clear how the high-order genome organization reshapes in cellular differentiation. Using Hi-C, we compared the comprehensive 3D genome maps in human embryonic stem cells (ESCs) and two differentiated cell types at kilobase resolution. Consistent with previous reports, we found that the CTCF protein anchors long-range constitutive interactions that are invariant between different cell types. The most stable DNA contacts in ESC are between a few hundred genomic loci with strongest histone H3 lysine 27 tri-methylation (H3K27me3) binding, which plays a key role maintaining pluripotency by inhibiting key development genes. These repressive 3D chromatin structures are resolved in differentiated cells, accompanied by redistribution of H3K27me3 mark. Most surprisingly, we found that in human ESCs, DNA looping interactions are not enriched at enhancers, suggesting a stochastic nature of DNA looping interactions at ESC enhancers. This is in sharp contrast to differentiated cells, in which a majority of cell type specific DNA looping interactions are at enhancers, regardless of whether the enhancers are co-occupied by CTCF. Taken together, our analysis revealed a primitive enhancer-independent genome architecture in ESCs, which is consistent with the stem cell pluripotency and differentiation plasticity. Most of the stable DNA looping interactions associated with lineage-governing enhancers are created only during cell fate commitment.

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Principles of 3D chromosome folding and evolutionary genome reshuffling in mammals

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A three-dimensional map of the human genome at kilobase resolution reveals prinicples of chromatin looping

Project description:We use in situ Hi-C to probe the three-dimensional architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1-kilobase resolution. We find that genomes are partitioned into local domains, which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ~10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs ‘facing’ one another. The inactive X-chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. in situ Hi-C and dilution Hi-C were used to probe the three-dimensional structure of the genome in eight diverse human cell types and one mouse cell type

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