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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Binding Sites / genetics
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase
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Humans
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism
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Models, Biological
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Interaction Domains and Motifs
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Homology, Amino Acid
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Trans-Activators / chemistry*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic*
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Transfection
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Zinc Fingers / genetics
Substances
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Intracellular Signaling Peptides and Proteins
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Kruppel-Like Transcription Factors
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Nuclear Proteins
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Recombinant Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase
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NSD1 protein, human