|Author||Christensen J, Agger K, Cloos PA, Pasini D, Rose S, Sennels L, Rappsilber J, Hansen KH, Salcini AE, Helin K.|
|Title||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.
|MeSH||Amino Acid Sequence Animals Caenorhabditis elegans / embryology Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / chemistry Carrier Proteins / genetics Carrier Proteins / metabolism* DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Drosophila melanogaster / enzymology Embryonic Stem Cells / enzymology Embryonic Stem Cells / metabolism Gene Deletion Genes, Homeobox Histone Demethylases Histones / metabolism* Humans Intracellular Signaling Peptides and Proteins / chemistry Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Jumonji Domain-Containing Histone Demethylases Lysine Methylation Mice Molecular Sequence Data Nuclear Proteins / chemistry Nuclear Proteins / genetics Nuclear Proteins / metabolism Oxidoreductases, N-Demethylating / chemistry Oxidoreductases, N-Demethylating / genetics Oxidoreductases, N-Demethylating / metabolism* Phylogeny Protein Structure, Tertiary Proteins / chemistry Proteins / genetics Proteins / metabolism Repressor Proteins / chemistry Repressor Proteins / genetics Repressor Proteins / metabolism Retinoblastoma-Binding Protein 2 Schizosaccharomyces / enzymology Sequence Alignment Tumor Suppressor Proteins / chemistry Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|