A5047484832- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Cleft Lip and Palate Research
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Craniofacial Disorders and Treatments
- Cancer-related gene regulation
- dental development and anomalies
- interferon and immune responses
- Genomics and Phylogenetic Studies
- Wireless Sensor Networks for Data Analysis
- Sensor Technology and Measurement Systems
- Plant Molecular Biology Research
- Fish biology, ecology, and behavior
- Nail Diseases and Treatments
- Axon Guidance and Neuronal Signaling
- Ubiquitin and proteasome pathways
- Skin and Cellular Biology Research
- Single-cell and spatial transcriptomics
University of Geneva
2022-2024
École Polytechnique Fédérale de Lausanne
2013-2024
Lawrence Berkeley National Laboratory
2020-2024
Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate origin phenotypic innovation by developing little skate Leucoraja erinacea as a genomically enabled model. Analysis high-quality chromosome-scale genome sequence for shows that it preserves many ancestral jawed vertebrate compared with other sequenced genomes,...
Hox genes are required during the morphogenesis of both vertebrate digits and external genitals. We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. show that same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting hijacking backbone from one context to other. In addition, comparable organizations observed at HoxA HoxD clusters, which separated through genome duplication an...
Abstract The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression genes during critical stages development. However, a lack accurate maps genomic locations cell type-resolved activities prevents their systematic exploration in genetics studies. Here, we combine histone modification, chromatin accessibility, gene profiling development with single-cell analyses...
In many animal species with a bilateral symmetry, Hox genes are clustered either at one or several genomic loci. This organization has functional relevance, as the transcriptional control applied to each gene depends upon its relative position within cluster. It was previously noted that vertebrate clusters display much higher level of than their invertebrate counterparts. The former always more compact latter, they generally devoid repeats and interspersed genes, all transcribed by same DNA...
The functionality of long noncoding RNAs (lncRNAs) is disputed. In general, lncRNAs are under weak selective pressures, suggesting that the majority may be nonfunctional. However, although some surveys showed negligible phenotypic effects upon lncRNA perturbation, key biological roles were demonstrated for individual lncRNAs. Most with proven functions implicated in gene expression regulation, pathways related to cellular pluripotency, differentiation, and organ morphogenesis, functional...
Polycomb group (PcG) proteins are essential for the repression of key factors during early development. In Drosophila, polycomb repressive complexes (PRC) associate with defined response DNA elements (PREs). mammals, however, mechanisms underlying recruitment at targeted loci poorly understood. We have used an in vivo approach to identify sequences importance proper HoxD locus. report that various genomic re-arrangements gene cluster do not strongly affect PRC2 and relatively small...
Genome-wide association studies for non-syndromic orofacial clefting (OFC) have identified single nucleotide polymorphisms (SNPs) at loci where the presumed risk-relevant gene is expressed in oral periderm. The functional subsets of such SNPs are difficult to predict because sequence underpinnings periderm enhancers unknown. We applied ATAC-seq models human palate periderm, including zebrafish mouse embryonic epithelia, and a epithelium cell line, complementary mesenchymal types. sets...
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 In this study, we report a unique and necessary function for the HoxC gene cluster in development of some ectodermal organs, as illustrated both by hair nail phenotype displayed mice lacking Hoxc13 congenital anonychia (absence nails) full mutants. We show that Hoxc genes are activated colinear manner embryonic limb ectoderm subsequently transcribed developing nails hairs. identify two mammalian-specific enhancers located upstream cluster, which display an exclusive specificity....
Mammalian tail length is controlled by several genetic determinants, among which are Hox13 genes, whose function to terminate the body axis. Accordingly, precise timing in transcriptional activation of these genes may impact upon length. Unlike other Hox clusters, HoxB lacks posterior between Hoxb9 and Hoxb13 , two separated a ca. 70 kb large DNA segment containing high number CTCF sites, potentially isolating from rest cluster thereby delaying its negative on trunk extension. We deleted...
Significance During development, transcription factors are necessary not only to pattern the body plan but also control growth. However, link between these two developmental components has been difficult establish. Hox genes involved in emergence of a functional digestive system metazoans, thus providing potential impact on growth through nutrition. Also, genetic conditions involving lead important retardation. We analyzed several targeted mutant lines at HoxD locus and found that stunted...
Skates are cartilaginous fish whose novel body plan features remarkably enlarged wing-like pectoral fins that allow them to thrive in benthic environments. The molecular underpinnings of this unique trait, however, remain elusive. Here we investigate the origin phenotypic innovation by developing little skate Leucoraja erinacea as a genomically enabled model. Analysis high-quality chromosome-scale genome sequence for shows it preserves many ancestral jawed vertebrate compared with other...
ABSTRACT In mammals, tail length is controlled by several genetic determinants, amongst which Hox13 genes located at the posterior extremities of Hox clusters, whose main function are to terminate extension body axis. this view, precise timing in transcriptional activation these may impact upon length. Unlike other HoxB lacks all between Hoxb9 and Hoxb13, two separated a ca. 70 kb large DNA segment containing an unusually high number CTCF sites, suggesting it isolates Hoxb13 from rest...
mutant mice are one of the rare strains that do not develop whisker hair follicles while still displaying a pelage. Here, we show
Abstract The precisely orchestrated differentiation of chondrocytes during skeleton development is a critical determinant human height and body shape disruptions this process can cause severe skeletal abnormalities. ultimate size each over 200 bones depends on the intricate spatiotemporal regulation chondrogenic chondrocyte genes, but genomic architecture coordinating these events remains poorly defined. Here we provide comprehensive map transcriptional enhancers specifically active in show...
Abstract Enhancer hijacking, a common cause of gene misregulation linked to disease, occurs when non-matching enhancers and promoters interact ectopically. This interaction is made possible by genetic changes that alter the arrangement or insulation regulatory landscapes. While concept enhancer hijacking well understood, specific reasons behind variation in phenotypic severity point at which those phenotypes become evident remain unexplored. In this work, we expand on ectopic activation...
Abstract Repertoires of transcriptional enhancers orchestrate gene expression during embryonic development, thereby shaping the forms and functions organs. Within these repertoires individual display spatially distinct or overlapping activities that collectively build up domain cognate genes. However, temporal specificity - how their change over developmental time to dynamically influence remains uncharacterized. Here, we observed temporally restricted enhancer are embedded at numerous loci...
Approximately a quarter of the human genome consists gene deserts, large regions devoid genes often located adjacent to developmental and thought contribute their regulation. However, defining regulatory functions embedded within these deserts is challenging due size. Here, we explore cis-regulatory architecture desert flanking Shox2 gene, which encodes transcription factor indispensable for proximal limb, craniofacial, cardiac pacemaker development. We identify as hub containing more than...
ABSTRACT Gene deserts are defined as genomic regions devoid of protein coding genes and spanning more than 500 kilobases, collectively encompassing about 25% the human genome. Approximately 30% all gene enriched for conserved elements with cis -regulatory signatures. These located predominantly near developmental transcription factors (TFs) but despite predicted critical functions, transcriptional contributions biological necessity most remain elusive. Here, we explore impact a desert...
The genetic basis of craniofacial birth defects and general variation in human facial shape remains poorly understood. Distant-acting transcriptional enhancers are a major category non-coding genome function have been shown to control the fine-tuned spatiotemporal expression genes during critical stages development