Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases

Johnathan R Whetstine; Amanda Nottke; Fei Lan; Maite Huarte; Sarit Smolikov; Zhongzhou Chen; Eric Spooner; En Li; Gongyi Zhang; Monica Colaiacovo; Yang Shi

doi:10.1016/j.cell.2006.03.028

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Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases

Journal article

Open access

Peer reviewed

Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases

Johnathan R Whetstine, Amanda Nottke, Fei Lan, Maite Huarte, Sarit Smolikov, Zhongzhou Chen, Eric Spooner, En Li, Gongyi Zhang, Monica Colaiacovo, …

Cell (Cambridge), Vol.125(3), pp.467-481

05/05/2006

DOI: 10.1016/j.cell.2006.03.028

PMID: 16603238

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Abstract

Histone 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.

Mutation

Meiosis - physiology

Histones - chemistry

Humans

Caenorhabditis elegans Proteins - metabolism

Oxidoreductases, N-Demethylating

DNA-Binding Proteins - metabolism

DNA Methylation

RNA Interference

Chromosomes - genetics

Chromosomes - metabolism

Germ Cells - cytology

Lysine - metabolism

Germ Cells - metabolism

Cell Differentiation - physiology

Rad51 Recombinase - metabolism

Catalytic Domain

Caenorhabditis elegans - metabolism

Rad51 Recombinase - genetics

Caenorhabditis elegans - genetics

Tumor Suppressor Protein p53 - metabolism

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Down-Regulation - physiology

Transcription Factors - metabolism

Animals

Caenorhabditis elegans - cytology

HeLa Cells

Histones - metabolism

Caenorhabditis elegans Proteins - genetics

Jumonji Domain-Containing Histone Demethylases

Details

Title: Subtitle: Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases
Creators: Johnathan R Whetstine - Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Amanda Nottke
Fei Lan
Maite Huarte
Sarit Smolikov
Zhongzhou Chen - University of Colorado Denver
Eric Spooner
En Li
Gongyi Zhang
Monica Colaiacovo
Yang Shi
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.125(3), pp.467-481
Publisher: United States
DOI: 10.1016/j.cell.2006.03.028
PMID: 16603238
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: R37 AI033456 / NIAID NIH HHS GM 071004 / NIGMS NIH HHS GM 072551 / NIGMS NIH HHS GM 58012 / NIGMS NIH HHS
Language: English
Date published: 05/05/2006
Academic Unit: Biology
Record Identifier: 9983992098802771

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