Diversity within the JMJD2 histone demethylase family.
JMJD2A-D belong to the JmjC domain-containing family of histone demethylases. JMJD2D is the most structurally divergent JMJD2 protein as it lacks the PHD and Tudor domains present in JMJD2A-C. Here, we systematically analyzed the histone demethylase specificity of JMJD2 proteins in vivo. We found that JMJD2A and C demethylate tri- and dimethylated H3K9 and H3K36, whereas JMJD2D demethylates tri-, di-, and monomethylated H3K9. Enzymatic activity requires the N-terminal JmjN domain. It also contributes to efficient nuclear localization together with the PHD and Tudor domains of JMJD2A and C. Furthermore, JMJD2 proteins form homomers, and JMJD2A and C, but not JMJD2D, can also heteromerize. Finally, we show that JMJD2 proteins promoter-specifically repress or activate gene transcription. Altogether, our results reveal novel properties of and functional differences between JMJD2 proteins that may therefore have different effects on chromatin structure.
Shin
Sook
S
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Guggenheim Building 1501A, 200 First Street SW, Rochester, MN 55905, USA.
Janknecht
Ralf
R
D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D006657:Histones; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases; D056484:Jumonji Domain-Containing Histone Demethylases; C494424:KDM4A protein, human; D010089:Oxidoreductases, N-Demethylating; D011495:Histone-Lysine N-Methyltransferase; C509186:TERT protein, human; D019098:Telomerase; D020781:Matrix Metalloproteinase 1; D008239:Lysine