Molecular Biology

Islands of Silence

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Science  17 Aug 2007:
Vol. 317, Issue 5840, pp. 872
DOI: 10.1126/science.317.5840.872b

In eukaryotes, DNA is packaged into chromatin, which serves as a platform for regulating access to the genome and modulating transcription, repair, and replication. Heterochromatin marks regions where, generally, genes are silenced; it is largely restricted to centromeres, the inactive X chromosome, and telomeres, and is thought to spread unless constrained by molecular barriers. Euchromatin, on the other hand, defines regions where genes are active. Yet silenced genes can be found among active genes. Do they exist as microdomains of heterochromatin, or are they some other form of repressive chromatin?

Regha et al. have examined the IgfR2 imprinted region on mouse chromosome 17. Here, the overlapping Air and Igf2r genes, with promoters a mere 28 kb apart, are reciprocally repressed on maternal and paternal chromosomes. Though silenced by different mechanisms—Air by DNA methylation and Igf2r via a noncoding RNA—the promoters of both genes bear highly localized marks on the histone components of their chromatin that match those found in classically defined regions of heterochromatin, specifically histone H4 trimethylated on lysine 20 (H4K20me3) and H3K9me3. Furthermore, these marks do not spread through the body of the gene. The results indicate that heterochromatin and euchromatin can be highly interspersed, even to the point where heterochromatin peaks can exist within the transcribed region of a neighboring active gene. In contrast, genes in regions that show tissue-specific repression are marked with broad swaths of H3K27me3, which delineates a second and perhaps long-term repressive chromatin state. — GR

Mol. Cell 27, 353 (2007).

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