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The largest family of transcription factors in mammals is of Cys(2)His(2) zinc finger-proteins, each with an NH(2)-terminal KRAB motif. Extensive expansions of this family have occurred in separate mammalian lineages, with approximately 400 such genes known in the human genome. Despite their widespread occurrence, the evolutionary provenance of the KRAB motif is unclear since previously it has not been found outside of the tetrapod vertebrates. Here, we show that homologues of the histone methyltransferase Meisetz are present within the sea urchin (Strongylocentrotus purpuratus) genome. Sea urchin and mammalian Meisetz sequences each contain an N-terminal KRAB motif, which thereby establishes an early origin of the KRAB motif prior to the divergence of echinoderm and chordate lineages. Finally, we present evidence that KRAB motifs derive from a novel family of KRI (KRAB Interior) motifs that were present in the last common ancestor of animals, plants and fungi.

Original publication




Journal article



Publication Date





2841 - 2845


Amino Acid Motifs, Animals, Base Sequence, Carrier Proteins, Chromosome Mapping, Evolution, Molecular, Histone-Lysine N-Methyltransferase, Mice, Molecular Sequence Data, Nuclear Proteins, Protein Methyltransferases, Repressor Proteins, Sea Urchins, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Transcription Factors