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Concept

Boîte homéotique

Publications associées (30)

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

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

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

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, Lucille Delisle, Guillaume Andrey, Christopher Chase Bolt

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

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

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

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, Lucille Delisle

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

HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

Alexandre Gauthier Aurèle Mayran

Hox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromat ...

Nature Research2020

Chromatin topology and the timing of enhancer function at the HoxD locus

Denis Duboule, Lucille Delisle

The HoxD gene cluster is critical for proper limb formation in tetrapods. In the emerging limb buds, different subgroups of Hoxd genes respond first to a proximal regulatory signal, then to a distal signal that organizes digits. These two regulations are e ...

National Academy of Sciences2020

Aurora A depletion reveals centrosome-independent polarization mechanism in Caenorhabditis elegans

Pierre Gönczy, Coralie Busso, Lukas von Tobel, Christian Gentili, Marie Juliette Ségolène Pierron, Kerstin Klinkert Fabbri

How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type Caenorhabditis elegans zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-direc ...

2019

Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch

The variability in transcription factor concentration among cells is an important developmental determinant, yet how variability is controlled remains poorly understood. Studies of variability have focused predominantly on monitoring mRNA production noise. ...

The Company of Biologists2019

Tail Bud Progenitor Activity Relies on a Network Comprising Gdf11, Lin28, and Hox13 Genes

Denis Duboule

During the trunk-to-tail transition, axial progenitors relocate from the epiblast to the tail bud. Here, we show that this process entails a major regulatory switch, bringing tail bud progenitors under Gdf11 signaling control. Gdf11 mutant embryos have an ...

Cell Press - Elsevier2019

Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes

Denis Duboule, Lucille Delisle

Background The spatial organization of the mammalian genome relies upon the formation of chromatin domains of various scales. At the level of gene regulation in cis, collections of enhancer sequences define large regulatory landscapes that usually match wi ...

2019

Coordinated Hoxd genes expression during embryogenesis is dependent on a strict disposition of genes and polarized regulators within the HoxD cluster

Fabrice Daniel Darbellay

HOX transcription factors determine the identity of body regions along the rostro-caudal axis during bilaterian embryogenesis. In vertebrates Hox genes distinctively lie organized in dense clusters, each typically composed of a dozen paralogous transcripti ...

EPFL2018

Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development

Denis Duboule, Marion Leleu

Background: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation ...

2018

Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Denis Duboule

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with larg ...

2017

Tissue-specific enhancer repression through molecular integration of cell signaling inputs

Bart Deplancke

Drosophila leg morphogenesis occurs under the control of a relatively well-known genetic cascade, which mobilizes both cell signaling pathways and tissue-specific transcription factors. However, their cross-regulatory interactions, deployed to refine leg p ...

2017

Control of growth and gut maturation by &ITHoxD&IT genes and the associated lncRNA &ITHaglr&IT

Denis Duboule, Fabrice Daniel Darbellay, Anamaria Necsulea

During embryonic development, Hox genes participate in the building of a functional digestive system in metazoans, and genetic conditions involving these genes lead to important, sometimes lethal,growth retardation. Recently, this phenotype was obtained af ...

National Academy of Sciences2017

Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Denis Duboule, Guillaume Andrey, Patrick Schorderet

During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood ...

National Academy of Sciences2017

The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes

Denis Duboule, Lucille Delisle

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas ...

2017

Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape

Denis Duboule, Guillaume Andrey, Anamaria Necsulea

Vertebrate Hox genes encode transcription factors operating during the development of multiple organs and structures. However, the evolutionary mechanism underlying this remarkable pleiotropy remains to be fully understood. Here, we show that Hoxd8 and Hox ...

National Academy of Sciences2016

Reorganisation of Hoxd regulatory landscapes during the evolution of a snake-like body plan

Denis Duboule

Within land vertebrate species, snakes display extreme variations in their body plan, characterized by the absence of limbs and an elongated morphology. Such a particular interpretation of the basic vertebrate body architecture has often been associated wi ...

Elife Sciences Publications Ltd2016