Publications by authors named "C Papin"
Histone variants are key epigenetic players, but their functional and physiological roles remain poorly understood. Here, we show that depletion of the histone variant H2A.Z in mouse skeletal muscle causes oxidative stress, oxidation of proteins, accumulation of DNA damages, and both neuromuscular junction and mitochondria lesions that consequently lead to premature muscle aging and reduced life span.
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- Inherited defects in the MBD4 gene increase the risk for adenomatous polyposis and colorectal cancer by causing a specific type of DNA damage known as C > T transitions.
- Research shows that MBD4 plays a crucial role in maintaining DNA methylation and repairing G/T mismatches, with its absence leading to widespread hypomethylation and transcriptional changes in genes and repetitive elements.
- The study concludes that MBD4 is essential for correcting deaminated 5-methylcytosines, highlighting its importance in protecting DNA from methylation-related damage in both healthy and diseased states.
CENP-A is an essential histone variant that replaces the canonical H3 at the centromeres and marks these regions epigenetically. The CENP-A nucleosome is the specific building block of centromeric chromatin, and it is recognized by CENP-C and CENP-N, two components of the constitutive centromere-associated network (CCAN), the first protein layer of the kinetochore. Recent proposals of the yeast and human (h)CCAN structures position the assembly on exposed DNA, suggesting an elusive spatiotemporal recognition.
View Article and Find Full Text PDFCholesterol 24-hydroxylase (CH24H, CYP46A1) is a cytochrome P450 family enzyme that maintains the homeostasis of brain cholesterol. Soticlestat, a potent and selective CH24H inhibitor, is in development as a therapeutic agent for Dravet syndrome and Lennox-Gastaut syndrome. Herein, we report the discovery of aryl-piperidine derivatives as potent and selective CH24H positron emission tomography (PET) tracers which can be used for dose guidance of a clinical CH24H inhibitor and as a diagnostic tool for CH24H-related pathology.
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- The histone variant H3.3, produced by two genes (H3f3a and H3f3b) with the same amino-acid sequence, is crucial for spermatogenesis, although its specific role was unclear.
- Research using genetically modified mice revealed that only H3.3B (not H3.3A) is essential for male fertility, affecting the transition during meiosis.
- Further analysis indicated that the absence of H3.3B causes changes in gene expression, notably increasing sex chromosome activity and altering piRNA cluster expression, highlighting H3.3B's significant regulatory role in spermatogenesis.