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ctcf, sites, pubmed, persistent, article, chromatin, binding, google, scholar, fig, cas, cell, data, cells, klk, boundaries, central, gene, tad, genome, lost, expression, performed, locus, nature, genes, rnai, domains, regions, chipseq, supplementary, depletion, region, dna, control, domain, min, cancer, types, tads, analysis, longrange, knockdown, lres, celltype, protein, active, bound, constitutive, boundary,

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nature portfolio privacy policy editing advertising long-range epigenetic-regulated domains �directionality index regional activation social media nature method protocol picard tools v1 medical research council reprints long-range epigenetic silencing long-range epigenetic remodeling long-range epigenetically active dna-tension-dependent barrier long-range epigenome expression paired nature long-range gene expression long-range chromatin interactions cell-type-specific domain boundaries author information authors enhancer/promoter function long-range deregulated region align chip-seq reads library-size quality medical research ctcf chip-seq data research design cloud-enabled peak caller analysed nome-seq data genome-wide chromatin effects adding 10 mm tris–hcl high-throughput data analysis encodes prostate-specific antigen peer review low salt buffer ctcf underlies evolution cell-type constitutive domains reporting summary serine-protease gene family observed/expected enrichment calculation long-distance chromatin interactions salmon sperm dna/protein cell-type-specific domains washu epigenome browser wild-type lncap cells31 auxin-inducible degron ctcf chip-qpcr assaying discrete ctcf-binding sites

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         headline:Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains
         description:The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The ‘persistent’ CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture. The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is regulated remains poorly understood. Here the authors find that there is a shared subset of CTCF-bound sites resistant to protein depletion in different cell lines, which are enriched at domain boundaries and chromatin loops constitutive to all cell types.
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      headline:Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains
      description:The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The ‘persistent’ CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture. The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is regulated remains poorly understood. Here the authors find that there is a shared subset of CTCF-bound sites resistant to protein depletion in different cell lines, which are enriched at domain boundaries and chromatin loops constitutive to all cell types.
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      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Fatima Valdes-Mora
      url:http://orcid.org/0000-0001-7490-0114
      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Phillippa C. Taberlay
      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:University of Tasmania
            address:
               name:School of Medicine, University of Tasmania, Hobart, Australia
               type:PostalAddress
            type:Organization
      name:Clare Stirzaker
      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:UNSW Sydney
            address:
               name:St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Aaron L. Statham
      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Susan J. Clark
      url:http://orcid.org/0000-0001-5925-5030
      affiliation:
            name:Garvan Institute of Medical Research
            address:
               name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
               type:PostalAddress
            type:Organization
            name:UNSW Sydney
            address:
               name:St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:School of Medicine, University of Tasmania, Hobart, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:Epigenetics Research, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia
      name:St Vincent’s Clinical School, UNSW Sydney, Sydney, Australia

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