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

Related publications (41)

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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

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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

Essential role of Cp190 in physical and regulatory boundary formation

Nicolas Jean Philippe Guex, Julien Dorier, Christian Iseli

Boundaries in animal genomes delimit contact domains with enhanced internal contact frequencies and have debated functions in limiting regulatory cross-talk between domains and guiding enhancers to target promoters. Most mammalian boundaries form by stalli ...

2022

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

Denis Duboule, Lucille Delisle, Christopher Chase Bolt, 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 ...

PUBLIC LIBRARY SCIENCE2021

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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

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Vertebrate genomes are partitioned into contact domains defined by enhanced internal contact frequency and formed by two principal mechanisms: compartmentalization of transcriptionally active and inactive domains, and stalling of chromosomal loop-extruding ...

2021

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

A complex regulatory landscape involved in the development of mammalian external genitals

Denis Duboule, Lucille Delisle, Christopher Chase Bolt

Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer-enhancer and enhancer-promoter interactions. ...

2020

Fryns type mesomelic dysplasia of the upper limbs caused by inverted duplications of the HOXD gene cluster

Denis Duboule

The HoxD cluster is critical for vertebrate limb development. Enhancers located in both the telomeric and centromeric gene deserts flanking the cluster regulate the transcription of HoxD genes. In rare patients, duplications, balanced translocations or inv ...

NATURE PUBLISHING GROUP2020

Hoxd genes are essential for the development of the various body axes in vertebrates and hence the underlying regulatory mechanisms are of paramount importance. Among these various mechanisms are long-range acting enhancers, which are located in the two ad ...

EPFL2019