Abstract
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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / physiology
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Carrier Proteins / metabolism*
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Chromosomes, Human, Pair 5
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Embryo, Mammalian / anatomy & histology
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Embryo, Mammalian / pathology
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Embryo, Mammalian / physiology*
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Embryonic Development*
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Female
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Gene Targeting
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Genes, Reporter
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase*
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Histones / metabolism
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Humans
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In Situ Hybridization
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In Situ Nick-End Labeling
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Intracellular Signaling Peptides and Proteins*
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Male
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Mesoderm / pathology
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Methylation
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Methyltransferases / metabolism
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Neoplasms / genetics
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Neoplasms / metabolism
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Nuclear Proteins / metabolism*
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Pregnancy
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Protein Methyltransferases
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / metabolism
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Sequence Alignment
Substances
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Carrier Proteins
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Histones
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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Recombinant Fusion Proteins
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Histone Methyltransferases
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Methyltransferases
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase
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NSD1 protein, human
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Nsd1 protein, mouse