Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex
Program in Gene Function and Expression
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.
DOI of Published Version
Nat Cell Biol. 2007 Oct;9(10):1167-74. Epub 2007 Sep 9. Link to article on publisher's site
Nature cell biology
Lanzuolo, Chiara; Roure, Virginie; Dekker, Job; Bantignies, Frederic; and Orlando, Valerio, "Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex" (2007). Program in Gene Function and Expression Publications and Presentations. 98.