Journal
NATURE CELL BIOLOGY
Volume 9, Issue 10, Pages 1167-1174Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1637
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Funding
- NHGRI NIH HHS [HG03143] Funding Source: Medline
- Telethon [TCR05001] Funding Source: Medline
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In Drosophila, the function of the Polycomb group genes ( PcGs) and their target sequences ( Polycomb response elements ( PREs)) is to convey mitotic heritability of transcription programmes-in particular, gene silencing. As part of the mechanisms involved, PREs are thought to mediate this transcriptional memory function by building up higher-order structures in the nucleus. To address this question, we analysed in vivo the three-dimensional structure of the homeotic locus bithorax complex ( BX-C) by combining chromosome conformation capture (3C) with fluorescent in situ hybridization ( FISH) and FISH immunostaining ( FISH-I) analysis. We found that, in the repressed state, all major elements that have been shown to bind PcG proteins, including PREs and core promoters, interact at a distance, giving rise to a topologically complex structure. We show that this structure is important for epigenetic silencing of the BX-C, as we find that major changes in higher-order structures must occur to stably maintain alternative transcription states, whereas histone modification and reduced levels of PcG proteins determine an epigenetic switch that is only partially heritable.
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