Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos

Article Article scientifique Article Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos eng 2023-06-15 2023-06-15 author Rekaik Hocine 0000-0002-6185-4777 909870 author Lopez-Delisle Lucille 0000-0002-1964-4960 author Hintermann Aurélie 745768 author Mascrez Bénédicte 0000-0002-9495-8556 644325 Département de génétique et évolution (Genev) (BIANI) author Bochaton Célia Corinne Renée 885897 author Mayran Alexandre 0000-0002-1228-0308 author Duboule Denis 0000-0001-9961-2960 28643 1164-1175 10.1038/s41588-023-01426-7 37322110 1061-4036 PMC10335938 https://www.nature.com/articles/s41588-023-01426-7 <p>During development, Hox genes are temporally activated according to their relative positions on their clusters, contributing to the proper identities of structures along the rostrocaudal axis. To understand the mechanism underlying this Hox timer, we used mouse embryonic stem cell-derived stembryos. Following Wnt signaling, the process involves transcriptional initiation at the anterior part of the cluster and a concomitant loading of cohesin complexes enriched on the transcribed DNA segments, that is, with an asymmetric distribution favoring the anterior part of the cluster. Chromatin extrusion then occurs with successively more posterior CTCF sites acting as transient insulators, thus generating a progressive time delay in the activation of more posterior-located genes due to long-range contacts with a flanking topologically associating domain. Mutant stembryos support this model and reveal that the presence of evolutionary conserved and regularly spaced intergenic CTCF sites controls the precision and the pace of this temporal mechanism.</p> Dewey 590 44 Département de génétique et évolution 162 false Nature genetics 55 7 f496118e-d708-4eaa-b566-f90fd65e1305 Article (Published version) Public Article-scientifique-from-crossref.pdf 18907480 application/pdf CC BY-4.0 b140f0832056110e583bf6528167e6cf8d1dd7b9e80643e99fadae16baccef76 openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution

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Sequential and directional insulation by conserved CTCF sites underlies the Hox timer in stembryos	Nature genetics			2023	38	27

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Bochaton, Célia Corinne Renée