NSD1 is essential for early post-implantation development and has a catalytically active SET domain

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 emb...

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Bibliographic Details
Published in:The EMBO journal 2003-06, Vol.22 (12), p.3153-3163
Main Authors: Chambon, Pierre, Rayasam, Geetha Vani, Wendling, Olivia, Angrand, Pierre-Olivier, Mark, Manuel, Niederreither, Karen, Song, Luyan, Lerouge, Thierry, Hager, Gordon L, Losson, Régine
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis - physiology
Biochemistry, Molecular Biology
Carrier Proteins - metabolism
Chromosomes, Human, Pair 5
Embryo, Mammalian - anatomy & histology
Embryo, Mammalian - pathology
Embryo, Mammalian - physiology
Embryonic Development
Female
gastrulation
gene disruption
Gene Targeting
Genes, Reporter
Histone-Lysine N-Methyltransferase
Histones - metabolism
HMTase
Humans
In Situ Hybridization
In Situ Nick-End Labeling
Intracellular Signaling Peptides and Proteins
Life Sciences
Male
Mesoderm - pathology
Methylation
Methyltransferases - metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neoplasms - genetics
Neoplasms - metabolism
Nuclear Proteins - metabolism
nuclear receptor cofactor
Pregnancy
Protein Methyltransferases
Protein Structure, Tertiary
Recombinant Fusion Proteins - metabolism
Sequence Alignment
SET domain
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Summary: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).
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/cdg288