Abstract
H3K9me2 and H3K27me2 are important epigenetic marks associated with transcription repression, while H3K4me3 is associated with transcription activation. It has been shown that active and repressive histone methylations distribute in a mutually exclusive manner, but the underlying mechanism was poorly understood. Here we identified ceKDM7A, a PHD (plant homeodomain)- and JmjC domain-containing protein, as a histone demethylase specific for H3K9me2 and H3K27me2. We further demonstrated that the PHD domain of ceKDM7A bound H3K4me3 and H3K4me3 co-localized with ceKDM7A at the genome-wide level. Disruption of the PHD domain binding to H3K4me3 reduced the demethylase activity in vivo, and loss of ceKDM7A reduced the expression of its associated target genes. These results indicate that ceKDM7A is recruited to the promoter to demethylate H3K9me2 and H3K27me2 and activate gene expression through the binding of the PHD domain to H3K4me3. Thus, our study identifies a dual-specificity histone demethylase and provides novel insights into the regulation of histone methylation.
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Acknowledgements
We thank Yang Shi (Harvard Medical School, USA) and Ruiming Xu (Institute of Biophysics, CAS, China) for their critical reading of the manuscript, the National BioResource Project for C. elegans (Japan) for the F29B9.2 (tm3713) mutant strain, the cell biology and molecular biology core facilities for MS and biacore experiments, and other members in Chen lab for technical help. This work was supported by grants from the National Basic Research Program of China (2010CB529700, 2009CB918600, and 2007CB947900), the National Natural Science Foundation of China (30870493, 90919026), Chinese Academy of Sciences (KSCX2-YW-R-04), Shanghai Pujiang Program (08PJ14010, 0757S11361), Shanghai Leading Academic Discipline Project (B111), and the Council of Shanghai Municipal Government for Science and Technology.
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( Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Figure S1
Mutation of H495 abolished the demethylase activity. (PDF 31 kb)
Supplementary information, Figure S2
Venn diagram of ceKDM7A and H3K4me3 bound genes identified by ChIP-Seq with the cutoff of one sequence tag. (PDF 12 kb)
Supplementary information, Table S1
Q-PCR analysis of gene expression comparing ceKDM7A knockout Tm3713 to wildtype N2. (PDF 21 kb)
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Lin, H., Wang, Y., Wang, Y. et al. Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res 20, 899–907 (2010). https://doi.org/10.1038/cr.2010.84
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DOI: https://doi.org/10.1038/cr.2010.84
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