Publications by authors named "Erwan Grandgirard"

The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites.

View Article and Find Full Text PDF
Article Synopsis
  • X-Linked myotubular myopathy (XLMTM) leads to significant muscle weakness and shorter life expectancy, with unclear impacts from non-muscular issues like liver problems.
  • Research using an Mtm1 mouse model involved RNA-sequencing to understand the disease's effects on skeletal muscles and to check heart and liver functions.
  • Findings showed skeletal muscle issues related to muscle development and inflammation, while the heart maintained function through compensatory mechanisms, suggesting potential areas for treatment focused on muscle defects in XLMTM.
View Article and Find Full Text PDF

To investigate the role of the nuclear receptor NR5A1 in the testis after sex determination, we analyzed mice lacking NR5A1 in Sertoli cells (SCs) from embryonic day (E) 13.5 onwards. Ablation of Nr5a1 impaired the expression of genes characteristic of SC identity (e.

View Article and Find Full Text PDF

The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unknown. We combine live tracking of genomic loci and nascent transcripts with molecular dynamics simulations to assess the spatiotemporal arrangement of the gene and its enhancer, in response to a battery of perturbations.

View Article and Find Full Text PDF

Hypothalamic AgRP/NPY neurons are key players in the control of feeding behaviour. Ghrelin, a major orexigenic hormone, activates AgRP/NPY neurons to stimulate food intake and adiposity. However, cell-autonomous ghrelin-dependent signalling mechanisms in AgRP/NPY neurons remain poorly defined.

View Article and Find Full Text PDF

The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unknown. We combine live tracking of genomic loci and nascent transcripts with molecular dynamics simulations to assess the 4D arrangement of the gene and its enhancer, in response to a battery of perturbations.

View Article and Find Full Text PDF

PLK1 is an important regulator of mitosis whose protein levels and activity fluctuate during the cell cycle. PLK1 dynamically localizes to various mitotic structures to regulate chromosome segregation. However, the signaling pathways linking localized PLK1 activity to its protein stability remain elusive.

View Article and Find Full Text PDF

Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment.

View Article and Find Full Text PDF

Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER-anchored proteins, such as MOSPD2, that function as major ER-organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain.

View Article and Find Full Text PDF

Mitochondria are highly dynamic organelles subjected to fission and fusion events. During mitosis, mitochondrial fission ensures equal distribution of mitochondria to daughter cells. If and how this process can actively drive mitotic progression remains largely unknown.

View Article and Find Full Text PDF
Article Synopsis
  • Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder that leads to motor incoordination due to the degeneration of the cerebellum, caused by mutations in the ATXN7 gene that involve polyglutamine expansion.
  • In a study using a new SCA7 knock-in mouse model, researchers found that gene expression changes significantly affected Purkinje cells, which are crucial for motor coordination, indicating that early gene downregulation contributes to severe motor and behavioral impairments.
  • The study reveals common molecular mechanisms across different types of spinocerebellar ataxias, suggesting potential therapeutic targets and shows that both male and female SCA7 mice exhibit key symptoms present in human
View Article and Find Full Text PDF

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by the presence of intranuclear inclusions of unknown origin. NIID is caused by an expansion of GGC repeats in the 5' UTR of the NOTCH2NLC (N2C) gene. We found that these repeats are embedded in a small upstream open reading frame (uORF) (uN2C), resulting in their translation into a polyglycine-containing protein, uN2CpolyG.

View Article and Find Full Text PDF