Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex
Program in Gene Function and Expression
Medical Subject Headings
Animals; Cell Line; Chromosomal Proteins, Non-Histone; Chromosomes; Drosophila; Drosophila Proteins; In Situ Hybridization, Fluorescence; Models, Biological; Protein Binding; Repressor Proteins; Response Elements; Transcription, Genetic
Genetics and Genomics
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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Citation: Nat Cell Biol. 2007 Oct;9(10):1167-74. Epub 2007 Sep 9. Link to article on publisher's site