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Chromatin three-dimensional interactions mediate genetic effects on gene expression

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Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

Johan Auwerx, Martin Rainer Wohlwend

Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with ...

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Background RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, we employ a systems approach to study ...

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Targeted Perturb-seq enables genome-scale genetic screens in single cells

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The transcriptome contains rich information on molecular, cellular and organismal phenotypes. However, experimental and statistical limitations constrain sensitivity and throughput of genetic screening with single-cell transcriptomics readout. To overcome ...

2020

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Expanded CAG/CTG repeats underlie 13 neurological disorders, including myotonic dystrophy type 1 (DM1) and Huntington's disease (HD). Upon expansion, disease loci acquire heterochromatic characteristics, which may provoke changes to chromatin conformation ...

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Observing protein interaction dynamics to chemically defined chromatin fibers by colocalization single-molecule fluorescence microscopy

Beat Fierz, Maxime Nicolas Mivelaz

In eukaryotic cells, the genome is packaged into chromatin and exists in different states, ranging from open euchromatic regions to highly condensed heterochromatic regions. Chromatin states are highly dynamic and are organized by an interplay of histone p ...

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TBX3 acts as tissue-specific component of the Wnt/beta-catenin transcriptional complex

Michel Aguet, Andreas Eduard Moor

BCL9 and PYGO are beta-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in de ...

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EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains

Suliana Manley, Elisa Oricchio, Kyle Michael Douglass, Daniele Tavernari, Natalya Katanayeva, Elena Battistello, Stephanie Jocelyne Sungalee, Maria Christine Donaldson, Timo Henry René Rey, Giovanni Ciriello, Marco Mina

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

Chromatin, the nucleoprotein complex organizing the genome, is central in regulating gene expression and genome organization. Chromatin conformational dynamics, controlled by histone post-translational modifications (PTM) and effector proteins, play a key ...

2019

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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

Histone Modifications in Development and Malignancy

Elisa Oricchio

Non-Hodgkin lymphoma (NHL) development is driven by the accumulations of multiple genetic, epigenetic, and chromosomal alterations. These lesions can lead to modifications of the chromatin architecture. To identify novel oncogenic interactions driven by mo ...

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