title: The function and regulation of the JARID1 family of histone H3 lysine 4 demethylases: the Myc connection.
abstract: Epigenetic regulation of transcription refers to reversible, heritable changes in gene expression that occur in the absence of changes in DNA sequence. A major epigenetic mechanism involves the covalent modification of nucleosomal histones to create binding sites for transcriptional regulators and chromatin remodeling complexes that mediate activation or repression of transcription. While it has been known for a number of years that many histone modifications are reversible, it has only recently been shown that methyl groups are enzymatically removed from lysine residues. Here we discuss the recent characterization of a new class of demethylase enzyme, the JARID1 family, which catalyzes the removal of methyl groups from lysine 4 of histone H3. We summarize recent findings regarding the function of this family of proteins, focusing on our characterization of Little imaginal discs (Lid), the sole JARID1 family protein in Drosophila, which is rate-limiting for Myc-induced cell growth. Finally, we propose models to explain the role of Lid in Myc-mediated growth and discuss the relevance of these findings to human disease and tumor formation.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Secombe
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D056466:Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D009707:Nucleosomes / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000145:classification / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012097:Repressor Proteins / Q000145:classification / Q000502:physiology*; D056485:Retinoblastoma-Binding Protein 2; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C070050:KDM5A protein, human; C119611:KDM5B protein, human; C518655:Lid protein, Drosophila; D056485:Retinoblastoma-Binding Protein 2; D010089:Oxidoreductases, N-Demethylating; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine