Reversal of Histone Lysine Trimethylation by the JMJD2 Family of Histone Demethylases

Autor: Yang Shi, Sarit Smolikov, Johnathan R. Whetstine, En Li, Maite Huarte, Eric Spooner, Gongyi Zhang, Amanda C. Nottke, Zhongzhou Chen, Fei Lan, Monica P. Colaiácovo
Rok vydání: 2006
Předmět:
Jumonji Domain-Containing Histone Demethylases
Histone lysine methylation
Down-Regulation
Biology
Chromosomes
General Biochemistry
Genetics and Molecular Biology
Histones
03 medical and health sciences
0302 clinical medicine
Histone demethylation
Histone H1
Catalytic Domain
Histone H2A
Histone methylation
Animals
Humans
Histone code
Caenorhabditis elegans
Caenorhabditis elegans Proteins
030304 developmental biology
0303 health sciences
Biochemistry
Genetics and Molecular Biology(all)
Lysine
Cell Differentiation
Oxidoreductases
N-Demethylating
DNA Methylation
DNA-Binding Proteins
Meiosis
Germ Cells
Biochemistry
030220 oncology & carcinogenesis
Histone methyltransferase
Mutation
RNA Interference
Rad51 Recombinase
Histone Demethylases
Tumor Suppressor Protein p53
HeLa Cells
Transcription Factors
Zdroj: Cell. 125:467-481
ISSN: 0092-8674
DOI: 10.1016/j.cell.2006.03.028
Popis: SummaryHistone methylation regulates chromatin structure, transcription, and epigenetic state of the cell. Histone methylation is dynamically regulated by histone methylases and demethylases such as LSD1 and JHDM1, which mediate demethylation of di- and monomethylated histones. It has been unclear whether demethylases exist that reverse lysine trimethylation. We show the JmjC domain-containing protein JMJD2A reversed trimethylated H3-K9/K36 to di- but not mono- or unmethylated products. Overexpression of JMJD2A but not a catalytically inactive mutant reduced H3-K9/K36 trimethylation levels in cultured cells. In contrast, RNAi depletion of the C. elegans JMJD2A homolog resulted in an increase in general H3-K9Me3 and localized H3-K36Me3 levels on meiotic chromosomes and triggered p53-dependent germline apoptosis. Additionally, other human JMJD2 subfamily members also functioned as trimethylation-specific demethylases, converting H3-K9Me3 to H3-K9Me2 and H3-K9Me1, respectively. Our finding that this family of demethylases generates different methylated states at the same lysine residue provides a mechanism for fine-tuning histone methylation.
Databáze: OpenAIRE
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