RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3.
Methylation of histones has been regarded as a stable modification defining the epigenetic program of the cell, which regulates chromatin structure and transcription. However, the recent discovery of histone demethylases has challenged the stable nature of histone methylation. Here we demonstrate that the JARID1 proteins RBP2, PLU1, and SMCX are histone demethylases specific for di- and trimethylated histone 3 lysine 4 (H3K4). Consistent with a role for the JARID1 Drosophila homolog Lid in regulating expression of homeotic genes during development, we show that RBP2 is displaced from Hox genes during embryonic stem (ES) cell differentiation correlating with an increase of their H3K4me3 levels and expression. Furthermore, we show that mutation or RNAi depletion of the C. elegans JARID1 homolog rbr-2 leads to increased levels of H3K4me3 during larval development and defects in vulva formation. Taken together, these results suggest that H3K4me3/me2 demethylation regulated by the JARID1 family plays an important role during development.
Christensen
Jesper
J
Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Agger
Karl
K
Cloos
Paul A C
PA
Pasini
Diego
D
Rose
Simon
S
Sennels
Lau
L
Rappsilber
Juri
J
Hansen
Klaus H
KH
Salcini
Anna Elisabetta
AE
Helin
Kristian
K
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000378:metabolism; D017353:Gene Deletion; D005801:Genes, Homeobox; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056485:Retinoblastoma-Binding Protein 2; D012568:Schizosaccharomyces / Q000201:enzymology; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C070050:KDM5A protein, human; C119611:KDM5B protein, human; C086877:KDM5C protein, human; C519283:RBR-2 protein, C elegans; D056485:Retinoblastoma-Binding Protein 2; D010089:Oxidoreductases, N-Demethylating; D008239:Lysine