NSD1 is essential for early post-implantation development and has a catalytically active SET domain.
Fiche publication
Date publication
juin 2003
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr MARK Manuel, Mr LEROUGE Thierry
Tous les auteurs :
Rayasam GV, Wendling O, Angrand PO, Mark M, Niederreither K, Song L, Lerouge T, Hager GL, Chambon P, Losson R
Lien Pubmed
Résumé
The nuclear receptor-binding SET domain-containing protein (NSD1) belongs to an emerging family of proteins, which have all been implicated in human malignancy. To gain insight into the biological functions of NSD1, we have generated NSD1-deficient mice by gene disruption. Homozygous mutant NSD1 embryos, which initiate mesoderm formation, display a high incidence of apoptosis and fail to complete gastrulation, indicating that NSD1 is a developmental regulatory protein that exerts function(s) essential for early post-implantation development. We have also examined the enzymatic potential of NSD1 and found that its SET domain possesses intrinsic histone methyltransferase activity with specificity for Lys36 of histone H3 (H3-K36) and Lys20 of histone H4 (H4-K20).
Mots clés
Amino Acid Sequence, Animals, Apoptosis, physiology, Carrier Proteins, metabolism, Chromosomes, Human, Pair 5, Embryo, Mammalian, anatomy & histology, Embryonic Development, Female, Gene Targeting, Genes, Reporter, Histone-Lysine N-Methyltransferase, Histones, metabolism, Humans, In Situ Hybridization, In Situ Nick-End Labeling, Intracellular Signaling Peptides and Proteins, Male, Mesoderm, pathology, Methylation, Methyltransferases, metabolism, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Neoplasms, genetics, Nuclear Proteins, metabolism, Pregnancy, Protein Methyltransferases, Protein Structure, Tertiary, Recombinant Fusion Proteins, metabolism, Sequence Alignment
Référence
EMBO J.. 2003 Jun;22(12):3153-63