A5013349042- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA regulation and disease
University of Geneva
2021-2024
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...
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 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...
ABSTRACT The expression of genes with a key function during development is frequently controlled by large regulatory landscapes containing multiple enhancer elements. These often match Topologically Associating Domains (TADs) and sometimes integrate range similar enhancers, thus leading to TADs having global specificity. To assess the relative functional importance sequences versus domain they are included in, we set out transfer one particular sequence from its native into TAD closely...
Abstract Most developmental genes rely on multiple transcriptional enhancers for their accurate expression during embryogenesis. Because may have partially redundant activities, the loss of one them often leads to a partial gene and concurrent moderate phenotypic outcome, if any. While such phenomenon has been observed in many instances, nature underlying mechanisms remains elusive. We used Pitx1 testbed locus characterize detail regulatory cellular identity alterations following deletion...