Chromosome topology guides the Dosage Compensation Complex for target gene activation.
Fiche publication
Date publication
août 2017
Journal
EMBO reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Schauer T, Ghavi-Helm Y, Sexton T, Albig C, Regnard C, Cavalli G, Furlong EE, Becker PB
Lien Pubmed
Résumé
X chromosome dosage compensation in requires chromosome-wide coordination of gene activation. The male-specific lethal dosage compensation complex (DCC) identifies and binds to X-chromosomal high-affinity sites (HAS) from which it boosts transcription. A sub-class of HAS, PionX sites, represent first contacts on the X. Here, we explored the chromosomal interactions of representative PionX sites by high-resolution 4C and determined the global chromosome conformation by Hi-C in sex-sorted embryos. Male and female X chromosomes display similar nuclear architecture, concordant with clustered, constitutively active genes. PionX sites, like HAS, are evenly distributed in the active compartment and engage in short- and long-range interactions beyond compartment boundaries. Long-range, inter-domain interactions between DCC binding sites are stronger in males, suggesting that the complex refines chromatin organization. By induction of DCC in female cells, we monitored the extent of activation surrounding PionX sites. This revealed a remarkable range of DCC action not only in linear proximity, but also at megabase distance if close in space, suggesting that DCC profits from pre-existing chromosome folding to activate genes.
Mots clés
chromatin, chromosome conformation capture, nuclear architecture
Référence
EMBO Rep.. 2017 Aug 9;: