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Association of differential and site-dependent CpG methylation and diverse expression of DNA methyltransferases with the tissue-specific expression of human β-globin gene in transgenic mice

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Abstract

Expression of human locus control region (LCR) and β-globin promoter has been recognized as an important factor in time- and tissue-specific expression event. DNA methylation can affect the transcriptional activity of specific genes. To investigate the methylation mechanism in the regulation of LCR and promote expression, this study used a transgenic mouse strain generated previously, in which the hematopoietic-specific expression of the EGFP was driven by human β-globin promoter and under the control of LCR, to examine the CpG methylation pattern in various tissues. The results showed the inverse correlation between the methylated extent and the levels of gene expression in all tested tissues. We also found that the methylated extent of the 10 examined CpG sites was biased along their positions and is more efficient near the transcription start site. Real-time quantitative RT-PCR analysis of DNA methyltransferases (DNMTs) transcripts showed that Dnmt3a and Dnmt3b expressed with a very low level in the hematopoietic tissues that was coincident with the relative higher EGFP expression in these tissues, indicating that the differential expression of DNMTs contributed to the tissue-specific methylated patterns which caused the diverse gene expression in various tissues. These findings provide significant clues to elucidate the mechanism of the regulation on tissue-specific expression of genes.

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Acknowledgments

This work was supported by Chinese National Program (Grant No. 2004CB518806, 2007AA02Z400), State and Shanghai Academic Leading Discipline (B204).

Conflict of interest statement

The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

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Authors and Affiliations

  1. Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Key Lab of Embryo Molecular Biology, Ministry of Health & Shanghai Lab of Reproduction and Embryo Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 24/1400 west Bei**g Road, 200040, Shanghai, People’s Republic of China

    Zhong-hai Yan, **u-li Gong, **n-bing Guo, Miao Xu, Zhao-rui Ren & Yi-tao Zeng

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  1. Zhong-hai Yan
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  2. **u-li Gong
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  3. **n-bing Guo
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Correspondence to Yi-tao Zeng.

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Yan, Zh., Gong, Xl., Guo, Xb. et al. Association of differential and site-dependent CpG methylation and diverse expression of DNA methyltransferases with the tissue-specific expression of human β-globin gene in transgenic mice. Int J Hematol 89, 414–421 (2009). https://doi.org/10.1007/s12185-009-0319-0

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  • DOI: https://doi.org/10.1007/s12185-009-0319-0

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