Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells

Epigenetics & Chromatin

Gangning Liang¹  Peter A Jones¹  Michael R Stallcup⁴  Shinwu Jeong¹  Han F Han³  Daniel S Gerke⁴  Shikhar Sharma² 

[1] Department of Urology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA;Program in Genetic, Molecular and Cellular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA;Department of Pharmacology and Pharmaceutical Sciences, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA;Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA

关键词: Epigenetics;    Maintenance;    Nucleosome;    DNA methylation;    DNMT3B;    DNMT3A;    G9a;   

Others  :  813825
DOI  :  10.1186/1756-8935-5-3

 received in 2011-08-25, accepted in 2012-01-27,  发布年份 2012

【 摘 要 】

Background

DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear.

Results

Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation.

Conclusions

Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.

【 授权许可】

   
2012 Sharma et al; licensee BioMed Central Ltd.

【 图 表 】

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