Matthieu Schapira

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UNLABELLED SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the(More)
The eight mammalian Cbx proteins are chromodomain-containing proteins involved in regulation of heterochromatin, gene expression, and developmental programs. They are evolutionarily related to the Drosophila HP1 (dHP1) and Pc (dPc) proteins that are key components of chromatin-associated complexes capable of recognizing repressive marks such as(More)
The MBT repeat has been recently identified as a key domain capable of methyl-lysine histone recognition. Functional work has pointed to a role for MBT domain-containing proteins in transcriptional repression of developmental control genes such as Hox genes. In this study, L3MBTL2, a human homolog of Drosophila Sfmbt critical for Hox gene silencing, is(More)
BACKGROUND Nicotine is a psychoactive drug presenting a diverse array of biological activities, some positive, such as enhancement of cognitive performances, others negative, such as addiction liability. Ligands that discriminate between the different isotypes of nicotinic acetylcholine receptors (nAChRs) could present improved pharmacology and toxicity(More)
UNLABELLED The rapidly increasing research activity focused on chromatin-mediated regulation of epigenetic mechanisms is generating waves of data on writers, readers and erasers of the histone code, such as protein methyltransferases, bromodomains or histone deacetylases. To make these data easily accessible to communities of research scientists coming from(More)
BACKGROUND Several Retinoic Acid Receptors (RAR) agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate(More)
There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state(More)
Histone methyltransferases (HMTs) transfer a methyl group from the cofactor S-adenosyl methionine to lysine or arginine residues on histone tails, thereby regulating chromatin compaction, binding of effector proteins and gene transcription. HMTs constitute an emerging target class in diverse disease areas, and selective chemical probes are necessary for(More)
WDR5 (WD40 repeat protein 5) is an essential component of the human trithorax-like family of SET1 [Su(var)3-9 enhancer-of-zeste trithorax 1] methyltransferase complexes that carry out trimethylation of histone 3 Lys4 (H3K4me3), play key roles in development and are abnormally expressed in many cancers. In the present study, we show that the interaction(More)
BACKGROUND Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets(More)