Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 916-924

Zeitschrift: Cell Cycle

Bandnummer: 8

Heftnummer: 6

ISSN: 1538-4101

eISSN: 1551-4005

Open Access Status: Bronze

DOI Link: https://doi.org/10.4161/cc.8.6.7934

Verlag: Taylor and Francis Group

Abstract: 

Differentiation and malignant transformation of stem cells are regulated by epigenetic mechanisms. We analyzed promoter methylation and expression of the stem cell determining genes Brachyury, DPPA5, FGF4, FOXD3, LIN28, NESTIN and ZFP42 depending on the differentiation state in human mesenchymal stem cells (MSC), human embryonal carcinoma cells (ECC) and somatic tumor cells. Differentiation of MSC into osteoblasts and adipocytes was accompanied with a loss of expression of the Brachyury gene and downregulation of LIN28. Inactivation of Brachyury was associated with progressive methylation of its CpG island promoter. In ECC promoter methylation of stem cell markers was more frequent in the differentiated subgroup (71%) compared to undifferentiated ECC (29%) and this was associated with downregulation of Brachyury, DPPA5, FGF4, FOXD3, LIN28 and ZFP42. DPPA5 was methylated and NESTIN was unmethylated in most tumor cells. In somatic tumor cells, methylation of stem cell markers (Brachyury, DPPA5, FGF4, FOXD3, LIN28 and ZFP42) was frequently observed (85%). Treatment of cell lines with an inhibitor of DNA methyltransferase reactivated the expression of DPPA5, FGF4, FOXD3, LIN28 and ZFP42, indicating that aberrant promoter methylation is a crucial event that results in their silencing. Our results suggest that epigenetic inactivation of stem cell associated genes is mediated by promoter methylation and that this may represent a fundamental mechanism during normal differentiation processes.

Harvard-Zitierstil: Dansranjavin, T., Krehl, S., Mueller, T., Mueller, L., Schmoll, H. and Dammann, R. (2009) The role of promoter CpG methylation in the epigenetic control of stem cell related genes during differentiation, Cell Cycle, 8(6), pp. 916-924. https://doi.org/10.4161/cc.8.6.7934

APA-Zitierstil: Dansranjavin, T., Krehl, S., Mueller, T., Mueller, L., Schmoll, H., & Dammann, R. (2009). The role of promoter CpG methylation in the epigenetic control of stem cell related genes during differentiation. Cell Cycle. 8(6), 916-924. https://doi.org/10.4161/cc.8.6.7934