Denis Duboule

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Comments on the Hox timer and related issues

In particular, this sequence is found in the 39 members of the amniote Hox gene family, a series of genes activated in mid-gastrulation and involved in organizing morphologies along the extending anterior to posterior (AP) body axis. Over the past 30 years ...

2025

Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos

Denis Duboule, Alexandre Gauthier Aurèle Mayran, Lucille Delisle

Understanding the interplay between cell fate specification and morphogenetic changes remains a challenge in developmental biology. Gastruloids, stem cell models of postimplantation mammalian development, provide a platform to address this question. Here, ...

American Association for the Advancement of Science (AAAS)2025

A CTCF-dependent mechanism underlies the Hox timer relation to a segmented body plan

Denis Duboule, Hocine Rekaik

During gastrulation, Hox genes are activated in a timesequence that follows the order of the genes along their clusters. This property, which is observed in all animals that develop following a progressive rostral-to-caudal morphogenesis, is associated wit ...

Current Biology Ltd2024

CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length

Denis Duboule, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Lucille Delisle, Fabrice Daniel Darbellay, Célia Corinne Renée Bochaton, Pierre Osteil

Mammalian tail length is controlled by several genetic determinants, among which are Hox13 genes, whose function is to terminate the body axis. Accordingly, the precise timing in the transcriptional activation of these genes may impact upon body length. Un ...

National Academy of Sciences2024

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

Denis Duboule, Alexandre Gauthier Aurèle Mayran, Hocine Rekaik, Célia Corinne Renée Bochaton, Lucille Delisle, Aurélie Hintermann

Temporal activation of Hox genes in mouse pseudo-embryos in vitro initiates at the anterior part of the cluster and is accompanied by asymmetric loading of cohesin. Posterior CTCF sites then successively act as transient insulators, regulating the timed tr ...

NATURE PORTFOLIO2023

Context-dependent enhancer function revealed by targeted inter-TAD relocation

Denis Duboule, Guillaume Andrey, Lucille Delisle, Christopher Chase Bolt, Aurélie Hintermann

Here the authors show that a strong enhancer sequence can be controlled by the chromatin environment provided by a topologically associated domain (TAD) located nearby. An enhancer relocated by homologous recombination takes all the hallmarks of its new ne ...

Nature Portfolio2022

The (unusual) heuristic value of Hox gene clusters; a matter of time?

Denis Duboule

Ever since their first report in 1984, Antennapedia-type homeobox (Hox) genes have been involved in such a series of interesting observations, in particular due to their conserved clustered organization between vertebrates and arthropods, that one may legi ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022

Mesomelic dysplasias associated with the HOXD locus are caused by regulatory reallocations

Denis Duboule, Christopher Chase Bolt, Lucille Delisle

Mesomelic dysplasia, a severe shortening and bending of the limb, has been linked to rearrangements in the HoxD cluster in humans and mice. Here the authors engineer a 1 Mb inversion including the HoxD gene cluster and use this model to provide a mechanist ...

Nature Portfolio2021

Sequential in cis mutagenesis in vivo reveals various functions for CTCF sites at the mouse HoxD cluster

Denis Duboule, Jozsef Zakany, Lucille Delisle, Leonardo Beccari

In this study, Amandio et al. sought to understand the functions of the highly conserved CTCF sites distributed over the Hox gene clusters. The authors produced an allelic series of cumulative in cis mutations in these sites, up to the abrogation of CTCF b ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2021

Induction of a chromatin boundary in vivo upon insertion of a tad border

Denis Duboule, Christopher Chase Bolt, Lucille Delisle, Edgardo Rodriguez Carballo, Marie-Laure Gadolini

Author summary During development, enhancer sequences tightly regulate the spatio-temporal expression of target genes often located hundreds of kilobases away. This complex process is made possible by the folding of chromatin into domains, which are separa ...

2021

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