Polycomb Repressive Complex 1 Generates Discrete Compacted Domains that Change during Differentiation

Sharmistha Kundu; Fei Ji; Hongjae Sunwoo; Gaurav Jain; Jeannie T Lee; Ruslan I Sadreyev; Job Dekker; Robert E Kingston

doi:10.1016/j.molcel.2017.01.009

Polycomb Repressive Complex 1 Generates Discrete Compacted Domains that Change during Differentiation

Mol Cell. 2017 Feb 2;65(3):432-446.e5. doi: 10.1016/j.molcel.2017.01.009.

Authors

Sharmistha Kundu¹, Fei Ji¹, Hongjae Sunwoo¹, Gaurav Jain², Jeannie T Lee³, Ruslan I Sadreyev⁴, Job Dekker⁵, Robert E Kingston⁶

Affiliations

¹ Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
² Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
³ Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
⁴ Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁵ Howard Hughes Medical Institute, Boston, MA 02115, USA; Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
⁶ Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kingston@molbio.mgh.harvard.edu.

Abstract

Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1). These domains changed during differentiation as PRC1 binding changed. Their formation depended upon the Polyhomeotic component of canonical PRC1 and occurred independently of PRC1-catalyzed ubiquitylation. PRC1 domains differ from topologically associating domains in size and boundary characteristics. These domains have the potential to play a key role in transmitting epigenetic silencing of PcG targets by linking PRC1 to formation of a repressive higher-order structure.

Keywords: 5C; PRC1; Polycomb; STORM; cell fate; chromatin; compaction; differentiation; higher-order structure.

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Chromatin / chemistry
Chromatin / genetics
Chromatin / metabolism
DNA / chemistry
DNA / genetics
DNA / metabolism*
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / metabolism
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Histones / metabolism
Homeodomain Proteins / metabolism
Humans
Mice
Neural Stem Cells / cytology*
Neural Stem Cells / metabolism
Polycomb Repressive Complex 1 / chemistry
Polycomb Repressive Complex 1 / metabolism*
Protein Domains
Ubiquitination

Substances

Chromatin
Histones
Homeodomain Proteins
DNA
Polycomb Repressive Complex 1

Abstract

MeSH terms

Substances

Grants and funding