A5047272346- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Genomic variations and chromosomal abnormalities
- Muscle Physiology and Disorders
- interferon and immune responses
- Congenital limb and hand anomalies
- Animal Genetics and Reproduction
- Plant Molecular Biology Research
- CRISPR and Genetic Engineering
- Cardiac Fibrosis and Remodeling
- RNA and protein synthesis mechanisms
- Neurological diseases and metabolism
- Icing and De-icing Technologies
- Ocular Diseases and Behçet’s Syndrome
- Mesenchymal stem cell research
- Cell Adhesion Molecules Research
- Physiological and biochemical adaptations
- Genetics, Aging, and Longevity in Model Organisms
- Biochemical effects in animals
- Pluripotent Stem Cells Research
- Signaling Pathways in Disease
University of Geneva
2019-2024
Max Planck Institute for Molecular Genetics
2015-2021
Charité - Universitätsmedizin Berlin
2018-2019
Berlin-Brandenburger Centrum für Regenerative Therapien
2019
École Polytechnique Fédérale de Lausanne
2013-2018
University Hospital of Bern
2018
University of Bern
2018
Federal Ministry of Science & Technology
2018
Yanka Kupala State University of Grodno
2012
University of Minnesota
2008
Hox genes are major determinants of the animal body plan, where they organize structures along both trunk and appendicular axes. During mouse limb development, Hoxd transcribed in two waves: early on, when arm forearm specified, later, digits form. The transition between late regulations involves a functional switch opposite topological domains. This is reflected by subset mapping centrally into cluster, which initially interact with telomeric domain subsequently swing toward centromeric...
Structural variations (SVs) contribute to the variability of our genome and are often associated with disease. Their study in model systems was hampered until now by labor-intensive genetic targeting procedures multiple mouse crossing steps. Here we present use CRISPR/Cas for fast (10 weeks) efficient generation SVs mice. We specifically produced deletions, inversions, also duplications at six different genomic loci ranging from 1.1 kb 1.6 Mb efficiencies up 42%. After PCR-based selection,...
Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of expression in space time. However, some cases, coincides with activation, whereas, others, preformed topologies already exist before activation. In this study, we investigate the configuration underlying
Complex regulatory landscapes control the pleiotropic transcriptional activities of developmental genes. For most genes, number, location, and dynamics their associated elements are unknown. In this work, we characterized three-dimensional chromatin microarchitecture landscape 446 limb-associated gene loci in mouse using Capture-C, ChIP-seq, RNA-seq forelimb, hindlimb at three stages, midbrain. The fine mapping interactions revealed a strong preference for functional genomic regions such as...
Homeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox are expressed in overlapping patterns and function a partially redundant manner. In vitro biochemical screens probing HOX-TF sequence specificity revealed largely preferences, indicating co-factors might modulate biological of HOX-TFs. However, due to their expression pattern, high protein homology, insufficiently specific antibodies, little is known about...
Significance During vertebrate evolution, Hox gene function was coopted through the emergence of global enhancers outside clusters. Here, we analyze regulatory modalities underlying Hoxd transcription into developing mammary glands where proteins are necessary. We report existence a long-distance acting bud enhancer located near sequences involved in controlling genes limbs. argue that particular constitutive chromatin structure found at this locus facilitated element mammals by hijacking...
In all tetrapods examined thus far, the development and patterning of limbs require activation gene members HoxD cluster. mammals, they are regulated by a complex bimodal process that controls first proximal then distal structure. During shift from former to latter regulation, this regulatory mechanism allows production domain with low Hoxd expression, at which both telomeric (T-DOM) centromeric domains (C-DOM) silent. These cells generate future wrist ankle articulations. We analyzed...
Abstract Developmental genes are frequently controlled by multiple enhancers sharing similar specificities. As a result, deletions of such regulatory elements have often failed to reveal their full function. Here, we use the Pitx1 testbed locus characterize in detail and cellular identity alterations following deletion one its ( Pen ). By combining single cell transcriptomics an in-embryo tracing approach, observe increased fraction non/low-expressing cells decreased high-expressing cells....
Abstract The expression of some genes depends on large, adjacent regions the genome that contain multiple enhancers. These regulatory landscapes frequently align with Topologically Associating Domains (TADs), where they integrate function similar enhancers to produce a global, TAD-specific regulation. We asked if an individual enhancer could overcome influence one these landscapes, drive gene transcription. To test this, we transferred from its native location, into nearby TAD related yet...
Abstract Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers show that they mechanistic framework through which non-coding genetic variants can influence skeletal human Working with fetal chondrocytes isolated from mice bearing Col2a1 fluorescent regulatory sensor, identify 780 genes 2'704 putative specifically active in using combination RNA-seq, ATAC-seq H3K27ac ChIP-seq. Most these (74%) pan...
Significance Because structures in the developing embryo are organized by secreted signals, embryonic cells must integrate multiple inputs to turn on target genes necessary for proper development. Little is known about how signals can work together regulate such an embryological context. In this work, we use cultured limb bud mesenchymal investigate two Sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8), control activity of Hoxd genes, a set transcription factors patterning tetrapod limbs.
Complex architectural rearrangements are associated to the control of HoxD genes in different cell types; yet, how they implemented single cells remains unknown. By use polymer models, we dissect locus 3D structure at DNA molecule level mouse embryonic stem and cortical neuronal cells, as cluster changes from a poised silent state. Our model describes published Hi-C, 3-way 4C, FISH data with high accuracy is validated against independent 4C on Nsi-SB 0.5-Mb duplication triple contacts. It...
The mechanism of pattern formation during limb muscle development remains poorly understood. canonical view holds that naïve progenitor cells (MPCs) invade a pre-established connective tissue, thereby forming individual muscles. Here we show early murine embryonic MPCs highly accumulate pSMAD1/5/9, demonstrating active signaling bone morphogenetic proteins (BMP) in these cells. Overexpression inhibitory SMAD6 abrogated BMP signaling, impaired their migration and proliferation, accelerated...
Abstract Mammalian genomes are scattered with transposable elements (TEs). TEs epigenetically silenced to prevent harmful effects caused by either global activation leading genome instability or insertional mutation disturbing gene transcription. However, whether the of a single element can contribute pathological phenotypes without directly affecting expression is largely unknown. Here, we show that tissue-specific TE in embryo leads production viral-like particles (VLPs) which affect organ...