Association of differential and site-dependent CpG methylation and diverse expression of DNA methyltransferases with the tissue-specific expression of human beta-globin gene in transgenic mice.
Expression of human locus control region (LCR) and beta-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 beta-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.
Yan
Zhong-Hai
ZH
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 Beijing Road, 200040, Shanghai, People's Republic of China.
Gong
Xiu-Li
XL
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 Beijing Road, 200040, Shanghai, People's Republic of China.
Guo
Xin-Bing
XB
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 Beijing Road, 200040, Shanghai, People's Republic of China.
Xu
Miao
M
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 Beijing Road, 200040, Shanghai, People's Republic of China.
Ren
Zhao-Rui
ZR
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 Beijing Road, 200040, Shanghai, People's Republic of China.
Zeng
Yi-Tao
YT
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 Beijing Road, 200040, Shanghai, People's Republic of China. ytzeng@stn.sh.cn.
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D055544:beta-Globins; D015254:DNA Modification Methylases