title: Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex.
abstract: 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.
authors.affiliation: Dulbecco Telethon Institute at IGB CNR, Epigenetics and Genome Reprogramming, Via Pietro Castellino 111, 80131 Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzuolo
authors.forename: Virginie
authors.initials: V
authors.lastname: Roure
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bantignies
authors.forename: Valerio
authors.initials: V
authors.lastname: Orlando
mesh_terms: D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008954:Models, Biological; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D014158:Transcription, Genetic