Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination.
Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of HOX gene clusters and regulates ... their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. Moreover, UTX associates with mixed-lineage leukemia (MLL) 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.
Mesh Terms:
Cell Differentiation, Cell Line, Cell Line, Tumor, DNA-Binding Proteins, Embryonic Stem Cells, Genes, Homeobox, Histones, Humans, Lysine, Methylation, Multigene Family, Neoplasm Proteins, Nuclear Proteins, Promoter Regions, Genetic, Protein Processing, Post-Translational, Recombinant Proteins, Repressor Proteins, Signal Transduction, Transcription, Genetic, Transcriptional Activation, Tretinoin, Ubiquitin
Cell Differentiation, Cell Line, Cell Line, Tumor, DNA-Binding Proteins, Embryonic Stem Cells, Genes, Homeobox, Histones, Humans, Lysine, Methylation, Multigene Family, Neoplasm Proteins, Nuclear Proteins, Promoter Regions, Genetic, Protein Processing, Post-Translational, Recombinant Proteins, Repressor Proteins, Signal Transduction, Transcription, Genetic, Transcriptional Activation, Tretinoin, Ubiquitin
Science
Date: Oct. 19, 2007
PubMed ID: 17761849
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