Biology subjects

Moyon, B.

Publications and source records attributed to Moyon, B..

4 recordsLinked to original sources

bioRxiv2026

Defective HIRA driven chromatin maintenance underlies age related decline in oocyte quality

The rapid fertility decline in women over 35 years of age has been attributed to decreasing oocyte quality. Aging oocytes accumulate DNA damage, chromosome segregation defects and altered epigenetic modifications. Critically, the molecular mechanisms underlying these changes remain poorly understood. Here we uncovered that in the mouse, the HIRA driven H3.3 histone replacement is attenuated during oocyte aging leading to the loss of chromatin homeostasis. The loss of HIRA function is caused by its SUMOylation resulting in the disruption of HIRA-UBN1-CABIN1 complex and its association with chromatin. We further show that preventing HIRA SUMOylation restores H3.3 incorporation and chromatin integrity in aged mouse oocytes leading to improved oocyte maturation and preimplantation development rates. Importantly, similar chromatin homeostasis defect is observed in aging human oocytes pointing towards a conserved process. Our findings provide novel insights into the molecular mechanisms underlying age-related oocyte quality decline and pave the way for clinical interventions.

developmental biology↗

bioRxiv2025

Inhibition of cytosolic DNA sensing and transposon activity safeguards pluripotency

Transposable elements (TEs) are mobile DNA sequences that make up a sizeable fraction of mammalian genomes yet are often tightly repressed by transcriptional and epigenetic mechanisms. During early development, epigenetic reprogramming selectively loosens TE repression, and TE transcription actively contributes to embryogenesis. This raises the question: how can embryos and embryonic stem cells (ESCs) tolerate TE expression without incurring widespread inflammation or DNA damage? Here, we reveal multiple mechanisms that prevent innate immune activation by TE-derived cytosolic DNA, including reduced cGAS/STING expression and signalling, dampening of Type I interferon responses by pluripotency factors, and post-transcriptional restriction of retrotransposition. These layers of protection are essential, as experimental perturbation triggers loss of ESC self-renewal and pluripotency. Our data explain how early development can be permissive to TE expression while safeguarding against harmful effects of TE activity.

developmental biology↗

bioRxiv2024

A dual enhancer-silencer element ensures transient Cdx2 expression during posterior body formation

During development, cells express precise gene expression programmes to assemble the trunk of the body plan. Appropriate control over the duration of the transcription factor Cdx2 is critical to achieve this outcome, yet, how cells control the onset, maintenance or termination of Cdx2, has remained unclear. Here, we delineate the cis-regulatory logic orchestrating dynamic Cdx2 expression in mouse caudal epiblast progenitors and their derivatives - spinal cord and presomitic mesoderm. Combining CRISPR-mediated deletion of regulatory elements with in vitro models and in vivo validation, we demonstrate that distinct enhancers, and a silencer, embedded at the Cdx2 locus, act sequentially to drive transient Cdx2 expression. We pinpoint a minimal silencer element that relies on a nuclear receptor motif to extinguish Cdx2. Changing this single motif converts the repressive element to an enhancer with opposite regulatory behaviour. Our findings elucidate design principles of developmental enhancers and silencers and establish a dual enhancer-silencer cis-regulatory logic ensuring precise spatiotemporal control over gene expression for vertebrate body patterning.

developmental biology↗

bioRxiv2019

Evolution of an amniote-specific mechanism for modulating ubiquitin signalling via phosphoregulation of the E2 enzyme UBE2D3

Genetic variation in the enzymes that catalyse post-translational modification of proteins is a potentially important source of phenotypic variation during evolution. Ubiquitination is one such modification that affects turnover of virtually all of the proteins in the cell in addition to roles in signalling and epigenetic regulation. UBE2D3 is a promiscuous E2 enzyme that acts as a ubiquitin donor for E3 ligases that catalyse ubiquitination of developmentally important proteins. We have used protein sequence comparison of UBE2D3 orthologues to identify a position in the C-terminal -helical region of UBE2D3 that is occupied by a conserved serine in amniotes and by alanine in anamniote vertebrate and invertebrate lineages. Acquisition of the serine (S138) in the common ancestor to modern amniotes created a phosphorylation site for Aurora B. Phosphorylation of S138 disrupts the structure of UBE2D3 and reduces the level of the protein in mouse ES cells (ESCs). Substitution of S138 with the anamniote alanine (S138A) increases the level of UBE2D3 in ESCs as well as being a gain of function early embryonic lethal in mice. When mutant S138A ESCs were differentiated into extra-embryonic primitive endoderm (PrE), levels of the PDGFR and FGFR1 receptor tyrosine kinases (RTKs) were reduced and PreE differentiation was compromised. Proximity ligation analysis showed increased interaction between UBE2D3 and the E3 ligase CBL and between CBL and the RTKs. Our results identify a sequence change that altered the ubiquitination landscape at the base of the amniote lineage with potential effects on amniote biology and evolution.

developmental biology↗