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The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth.

Secombe, Julie and Li, Ling and Carlos, Leni and Eisenman, Robert N (2007) The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth. Genes & development, 21 (5). pp. 537-551. ISSN 0890-9369

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The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc's transcriptional specificity remain elusive. We have carried out a genetic screen in Drosophila and identified the Trithorax group protein Little imaginal discs (Lid) as a regulator of dMyc-induced cell growth. Lid binds to dMyc and is required for dMyc-induced expression of the growth regulatory gene Nop60B. The mammalian Lid orthologs, Rbp-2 (JARID1A) and Plu-1 (JARID1B), also bind to c-Myc, indicating that Lid-Myc function is conserved. We demonstrate that Lid is a JmjC-dependent trimethyl H3K4 demethylase in vivo and that this enzymatic activity is negatively regulated by dMyc, which binds to Lid's JmjC domain. Because Myc binding is associated with high levels of trimethylated H3K4, we propose that the Lid-dMyc complex facilitates Myc binding to, or maintenance of, this chromatin context.

Item Type: Article or Abstract
Additional Information: This article is freely available in PubMed Central and at the journal's website.
DOI: 10.1101/gad.1523007
PubMed ID: 17311883
PMCID: PMC1820896
Grant Numbers: CA57138
Keywords or MeSH Headings: Animals; Cell Proliferation; Chromosomal Proteins, Non-Histone/metabolism; DNA-Binding Proteins/genetics/metabolism; Drosophila Proteins/chemistry/genetics/metabolism; Drosophila melanogaster/embryology/genetics/metabolism; Eye/cytology/embryology/innervation; Female; Gene Expression Regulation, Developmental; Genes, Insect; Histone-Lysine N-Methyltransferase/chemistry/genetics/metabolism; Hydro-Lyases/metabolism; Male; Mutation; Neurons/cytology; Nuclear Proteins/metabolism; Phenotype; Protein Structure, Tertiary; Proto-Oncogene Proteins c-myc/genetics/metabolism; Transcription Factors/genetics/metabolism;
Subjects: Molecules > Proteins > Transcription factors
Cellular and Organismal Processes > Cell Physiology > Cell proliferation
Molecules > Genes > Oncogenes
Depositing User: Library Staff
Date Deposited: 10 Dec 2008 22:51
Last Modified: 24 May 2010 18:42

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