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

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Science  10 Mar 2017:
Vol. 355, Issue 6329, pp. 1081-1084
DOI: 10.1126/science.aah5403

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Polycomb group gene silencing

Histone proteins wrap around DNA to form nucleosomes that package metazoan DNA into the nucleus. Chromatin compaction is also believed to be critical for the repression of homeotic genes by the Polycomb repressive complex 1 (PRC1) during development. Lau et al. used mutagenesis and expression analyses to examine this gene silencing mechanism. Altering the PRC1 compaction region affected transcriptional repression and patterning of the mouse body axis. Thus, chromatin compaction may drive the stable and heritable silencing of genes involved in body patterning.

Science, this issue p. 1081


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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