title: Mutation of a nucleosome compaction region disrupts Polycomb-mediated axial patterning.
abstract: Nucleosomes play important structural and regulatory roles by tightly wrapping the DNA that constitutes the metazoan genome. The Polycomb group (PcG) proteins modulate nucleosomes to maintain repression of key developmental genes, includingHoxgenes whose temporal and spatial expression is tightly regulated to guide patterning of the anterior-posterior body axis. CBX2, a component of the mammalian Polycomb repressive complex 1 (PRC1), contains a compaction region that has the biochemically defined activity of bridging adjacent nucleosomes. Here, we demonstrate that a functional compaction region is necessary for proper body patterning, because mutating this region leads to homeotic transformations similar to those observed with PcG loss-of-function mutations. We propose that CBX2-driven nucleosome compaction is a key mechanism by which PcG proteins maintain gene silencing during mouse development.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mei Sheng
authors.identifier: 0000-0002-7867-9426
authors.initials: MS
authors.lastname: Lau
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew G
authors.identifier: 0000-0001-9549-9868
authors.initials: MG
authors.lastname: Schwartz
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrej J
authors.initials: AJ
authors.lastname: Savol
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peggy I
authors.identifier: 0000-0003-1504-6370
authors.initials: PI
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Marr
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Grau
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schorderet
authors.affiliation: 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.
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Sadreyev
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Clifford J
authors.identifier: 0000-0002-2957-4871
authors.initials: CJ
authors.lastname: Tabin
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. kingston@molbio.mgh.harvard.edu.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert E
authors.identifier: 0000-0003-3628-4335
authors.initials: RE
authors.lastname: Kingston
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005801:Genes, Homeobox; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012863:Skeleton / Q000254:growth & development
chemical_list: C570426:Cbx2 protein, mouse; D009707:Nucleosomes; D063150:Polycomb Repressive Complex 1