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Stem Cells

Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells

Leukemia volume 20, pages 1551–1556 (2006)Cite this article

Abstract

CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription. Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat. There are CpG sequences around the promoter of CDCP1, which were heavily methylated in Jurkat but not in K562. Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter. Among normal hematopoietic cells such as CD34+CD38− cells, lymphocytes and granulocytes, inverse correlation between proportion of methylated CpG sequences and CDCP1 expression level was found. Demethylation of CpG sequences in lymphocytes, in which CpG sequences were heavily methylated, induced CDCP1 expression and its expression level further increased through zfp67 overexpression. The methylation of DNA appeared to regulate the cell-type-specific expression of CDCP1 through the control of interaction between chromatin DNA and transcription factors.

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Acknowledgements

We thank Mr M Kohara, Ms M Sugano and Ms T Sawamura (Osaka University) for technical supports. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, and from the Osaka Cancer Research Foundation.

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Authors and Affiliations

  1. Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    H Kimura, E Morii, J-i Ikeda, J-X Xu, N Nakamichi, Y Tomita & K Aozasa

  2. Department of Hematology/Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    S Ezoe, H Shibayama & Y Kanakura

  3. 1st Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan

    N Nakamichi

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  1. H Kimura
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Correspondence to E Morii.

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Kimura, H., Morii, E., Ikeda, Ji. et al. Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells. Leukemia 20, 1551–1556 (2006). https://doi.org/10.1038/sj.leu.2404312

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