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CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription

ABSTRACT: Spatial genome organization and its effect on transcription remains a fundamental biological question. We applied an advanced ChIA-PET strategy to comprehensively map higher-order chromosome folding and chromatin interactions mediated by CTCF and RNAPII with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes towards CTCF-foci and forming RNAPII foci for coordinated transcription. Furthermore, allelic-variants linked to disease susceptibility are found to impact chromatin topology and transcriptional regulation. Importantly, 3D-genome simulation suggested a model of chromatin folding around chromosomal axes, where CTCF involves in defining the interface between condensed and open compartments for structural regulation. Our new 3D-genome strategy thus provides novel insights to explore the topological mechanism of human variations and diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE72816 | GEO | 2015/12/11

SECONDARY ACCESSION(S): PRJNA295132

REPOSITORIES: GEO

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