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Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients

  • Original Article—Alimentary Tract
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Abstract

Background

Trimethylation of histone H3 lysine 27 (H3K27me3) is a posttranslational modification that is highly correlated with genomic silencing. In gastric cancer (GC), global and gene-specific DNA methylation changes have been demonstrated to occur. However, to date, our understanding of the alterations in H3K27me3 in GC is incomplete. This study aimed to investigate the variations in H3K27me3 in CpG island regions between gastric cancerous and matched non-cancerous tissues.

Methods

H3K27me3 variations were analyzed in eight pairs of GC and adjacent normal tissues, from eight GC patients, using a chromatin immunoprecipitation linked to the microarray (ChIP-chip) approach. ChIP–real time PCR was used to validate the microrray results. In addition, DNA methylation status also was further analyzed by methyl-DNA immunoprecipitation quantitative PCR.

Results

One hundred twenty-eight (119 increased and 9 decreased H3K27me3) genes displaying significant H3K27me3 differences were found between GC and adjacent normal tissues. The results of ChIP–real time PCR coincided well with those of microarray. Aberrant DNA methylation can also be found on selected randomly positive genes (MMP15, UNC5B, SHH, AFF3, and RB1).

Conclusion

Our study indicates that there are significant alterations of H3K27me3 in gastric cancerous tissues, which may help clarify the molecular mechanisms involved in the pathogenesis of GC. Such novel findings show the significance of H3K27me3 as a potential biomarker or promising target for epigenetic-based GC therapies.

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Acknowledgments

The authors thank the patients who participated in this study.

Author information

Authors and Affiliations

  1. The Second Clinical Medical College, Jinan University, Guangdong, China

    Li Zhang, Keli Zhong, Yong Dai & Hanxin Zhou

  2. Shenzhen People’s Hospital, 1017, North Road, Dongmen, Shenzhen, 518020, Guangdong, People’s Republic of China

    Yong Dai

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  1. Li Zhang
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  2. Keli Zhong
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  3. Yong Dai
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  4. Hanxin Zhou
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Corresponding author

Correspondence to Yong Dai.

Additional information

L. Zhang and K. Zhong contributed equally to this report.

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Zhang, L., Zhong, K., Dai, Y. et al. Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients. J Gastroenterol 44, 305–312 (2009). https://doi.org/10.1007/s00535-009-0027-9

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  • DOI: https://doi.org/10.1007/s00535-009-0027-9

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