Mutation of a nucleosome compaction region disrupts Polycomb-mediated axial patterning

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, including Hox genes whose temporal and spatial expression is tightly...

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Published inScience (American Association for the Advancement of Science) Vol. 355; no. 6329; pp. 1081 - 1084
Main Authors Lau, Mei Sheng, Schwartz, Matthew G., Kundu, Sharmistha, Savol, Andrej J., Wang, Peggy I., Marr, Sharon K., Grau, Daniel J., Schorderet, Patrick, Sadreyev, Ruslan I., Tabin, Clifford J., Kingston, Robert E.
Format Journal Article
LanguageEnglish
Published United States American Association for the Advancement of Science 10.03.2017
The American Association for the Advancement of Science
Subjects
Animals
Biochemistry
Body Patterning - genetics
Cell Line
Chromatin
Compaction
Deoxyribonucleic acid
DNA
Gene expression
Gene Expression Regulation, Developmental
Gene regulation
Gene Silencing
Genes
Genes, Homeobox
Genomes
Metazoa
Mice
Mice, Mutant Strains
Mutation
Mutations
Nucleosomes - genetics
Nucleosomes - metabolism
Patterning
Polycomb Repressive Complex 1 - genetics
Polycomb Repressive Complex 1 - metabolism
Protein Binding
Proteins
Skeleton - growth & development
Transformations
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Summary: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, including Hox genes 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.
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These authors contributed equally to this work.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.aah5403