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  • The EMBO Journal (2003) 22, 3153 - 3163
  • doi:10.1093/emboj/cdg288

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

Geetha Vani Rayasam1, Olivia Wendling2, Pierre-Olivier Angrand3, Manuel Mark2, Karen Niederreither4, Luyan Song2, Thierry Lerouge2, Gordon L. Hager1, Pierre Chambon2,5 and Régine Losson2,5

  1. Laboratory of Receptor Biology and Gene Expression, National Institutes of Health, Bethesda, MD 20892, USA
  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP 10142, 67404 Illkirch-Cedex, France
  3. Cellzome AG, Meyerhofstr. 1, D-69117 Heidelberg, Germany
  4. Departments of Medicine and Molecular and Cellular Biology, Center for Cardiovascular Development, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
  5. P.Chambon and R.Losson contributed equally to this work

Correspondence to:

Pierre Chambon, E-mail: chambon@igbmc.u-strasbg.fr

Received 30 September 2002; Accepted 17 April 2003; Revised 10 April 2003

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).

  • Keywords:

    • gastrulation,
    • gene disruption,
    • HMTase,
    • nuclear receptor cofactor,
    • SET domain