Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation

Author:

Kraft Katerina1,Yost Kathryn E.1,Murphy Sedona E.2,Magg Andreas34,Long Yicheng567,Corces M. Ryan1,Granja Jeffrey M.12,Wittler Lars8ORCID,Mundlos Stefan34,Cech Thomas R.567ORCID,Boettiger Alistair N.9,Chang Howard Y.110ORCID

Affiliation:

1. Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305

2. Department of Genetics, Stanford University, Stanford, CA 94305

3. Research Group of Development and Disease, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany

4. Institute for Medical and Human Genetics, Charité Universitätsmedizin, 10117 Berlin, Germany

5. HHMI, University of Colorado, Boulder, CO 80309

6. Department of Biochemistry, University of Colorado, Boulder, CO 80309

7. BioFrontiers Institute, University of Colorado, Boulder, CO 80309

8. Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany

9. Department of Developmental Biology, Stanford University, Stanford, CA 94305

10. HHMI, Stanford University School of Medicine, Stanford, CA 94305

Abstract

Significance The relationship between long-range Polycomb-associated chromatin contacts and the linear propagation of histone H3 lysine 27 trimethylation (H3K27me3) by Polycomb repressive complex 2 (PRC2) is not well-characterized. Here, we nominate a role for developmental loci as genomic architectural elements that enable long-range spreading of H3K27me3. Polycomb-associated loops are disrupted upon loss of PRC2 binding and deletion of loop anchors results in alterations of H3K27me3 deposition and ectopic gene expression. These results suggest that Polycomb-mediated genome architecture is important for gene repression during embryonic development.

Funder

Foundation for the National Institutes of Health

Deutsche Forschungsgemeinschaft

National Science Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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