A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus

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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

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

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

CTCF loss has limited effects on global genome architecture in Drosophila despite critical regulatory functions

Christian Iseli, Nicolas Jean Philippe Guex, Julien Dorier, Flavia Marzetta

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 ...

Nature Research2021

Toward a mechanistic understanding of variable chromatin modules

Gerard Llimos Aubach

Our genome is a long sequence of DNA that contains all the information to be able to constitute a living organism like us, similarly to what the letters in a book do to create a story. This sequence, which is a stretch of molecules called nucleotides, is a ...

EPFL2021

The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benjamin Marcel Daniel Rothé

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic inte ...

Nature Research2021

Chromatin Proteomics to Study Epigenetics - Challenges and Opportunities

Guido Van Mierlo

Regulation of gene expression is essential for the functioning of all eukaryotic organisms. Understanding gene expression regulation requires determining which proteins interact with regulatory elements in chromatin. MS-based analysis of chromatin has emer ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2021

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Natalya Katanayeva, Daniele Tavernari, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta, Giovanni Ciriello

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

Notch1-driven T-ALL chromatin landscape is regulated by Tcf1 in hematopoietic progenitors

Mateusz Waldemar Antoszewski

Notch1 receptor signaling is essential for T cell fate specification and physiological thymic T lymphocyte development. Its dysregulation and oncogenic activation are detected in almost 80% of pediatric patients suffering from T cell acute lymphoblastic le ...

EPFL2021

Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle

Felix Naef, Jake Yeung, Jérôme Mermet

The circadian clock drives extensive temporal gene expression programs controlling daily changes in behavior and physiology. In mouse liver, transcription factors dynamics, chromatin modifications, and RNA Polymerase II (PolII) activity oscillate throughou ...

2021

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The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benjamin Marcel Daniel Rothé

Nature Research2021