The NIZP1 KRAB and C2HR domains cross-talk for transcriptional regulation

Biochim Biophys Acta. 2010 May-Jun;1799(5-6):463-8. doi: 10.1016/j.bbagrm.2010.02.003. Epub 2010 Feb 20.

Abstract

The NSD1 histone methyltransferase is involved in the outgrowth disorders Sotos and Weaver syndromes and childhood acute myeloid leukemia. NSD1 is a bona fida transcriptional co-repressor for Nizp1 which is a protein including SCAN, KRAB, C2HR and zinc-finger domains. In this study the Nizp1 KRAB-domain was identified to possess an intrinsic transcriptional activation capacity suppressed in cis by the presence of the C2HR domain. Oppositely, the KRAB-domain supported C2HR domain mediated transcriptional repression. The presence of the KRAB-domain resulted in increased NSD1 co-repressor association with the C2HR domain. This study shows a new function of the KRAB-domain, C2HR-domain, and the associated factors to confer Nizp1 mediated transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic*
  • Transfection
  • Zinc Fingers / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD1 protein, human