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

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Any living organism contains a whole set of instructions encoded as genes on the DNA. This set of instructions contains all the necessary information that the organism will ever need, from its development to a mature individual to environment specific resp ...

EPFL2020

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

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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

Analysis of long-range gene regulation at the HoxD locus

Ana Rita De Carvalho Amândio Lhopitallier

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

A Tale of Two Tumors: Unraveling the Complexities of Epigenetic Dysregulation in Cancer

Maria Christine Donaldson

Epigenetics plays an important role in cancer development and progression. Cancer cells hijack the epigenome by modifying the histone protein units responsible for packaging DNA, or by modifying the DNA itself, resulting in changes to chromatin topology an ...

EPFL2019

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Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks. In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 L ...

2019

Opposing chromatin remodelers control transcription initiation frequency and start site selection

Philipp Bucher, René Dreos

Precise nucleosome organization at eukaryotic promoters is thought to be generated by multiple chromatin remodeler (CR) enzymes and to affect transcription initiation. Using an integrated analysis of chromatin remodeler binding and nucleosome occupancy fol ...

NATURE PUBLISHING GROUP2019

Similarities and differences in the regulation of HoxD genes during chick and mouse limb development

Denis Duboule, Lucille Delisle, Guillaume Andrey, Leonardo Beccari, Christopher Chase Bolt, Nayuta Yakushiji

In all tetrapods examined thus far, the development and patterning of limbs require the activation of gene members of the HoxD cluster. In mammals, they are regulated by a complex bimodal process that controls first the proximal patterning and then the dis ...

PUBLIC LIBRARY SCIENCE2018

What shapes eukaryotic transcriptional bursting?

Felix Naef, Damien Lionel Nicolas, Nicholas Edward Phillips

Isogenic cells in a common environment present a large degree of heterogeneity in gene expression. Part of this variability is attributed to transcriptional bursting: the stochastic activation and inactivation of promoters that leads to the discontinuous p ...

Royal Society of Chemistry2017

Rhythmic and clock-dependent chromatin loops regulate circadian gene expression

Jérôme Mermet

In mammals the circadian clock drives daily behavioural and physiological changes that resonate with environmental cues, which can be observed, for example, in the intricate timing of rest during the night and activity during the day in humans. The circadi ...

EPFL2017