tailieunhanh - Báo cáo khoa học: Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements

DNA methylation is an important mechanism involved in embryogenesis and tumor development. Changing cytosines to 5-methylcytosines in CpG dinucleotides has been found to be responsible for the inactivation of tumor suppressor genes by repressing transcription. | ỊFEBS Journal Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements Katrin Tschop1 2 3 and Kurt Engeland1 2 4 1 Interdisziplinares Zentrum fur Klinische Forschung Medizinische Fakultat Universitat Leipzig Germany 2 Zentrum fur Innere Medizin Medizinische Fakultejf Universitat Leipzig Germany 3 Klinik fur Hals- Nasen- Ohrenheilkunde Medizinische Fakultat Universitat Leipzig Germany 4 Frauenklinik Medizinische Fakultat Universitat Leipzig Germany Keywords cell cycle CpG island cyclin B DNA methylation promoter Correspondence K. Engeland Medizinische Fakultejt Universitat Leipzig Philipp-Rosenthal Str. 55 D-04103 Leipzig Germany Fax 49 341 9723409 Tel 49 341 9725900 E-mail engeland@ Received 24 May 2007 revised 3 August 2007 accepted 15 August 2007 doi DNA methylation is an important mechanism involved in embryogenesis and tumor development. Changing cytosines to 5-methylcytosines in CpG dinucleotides has been found to be responsible for the inactivation of tumor suppressor genes by repressing transcription. A central cell cycle regulator whose synthesis is controlled by transcription is cyclin B. In mammalian cells cyclin B1 and B2 proteins are well characterized and often found to be overexpressed in cancer patients. Transcription from cyclin B1 and B2 promoters during the cell cycle is dependent upon a combination of two sites named cell cycle-dependent element CDE and cell cycle genes homology region CHR through repression in G0 and G followed by release in G2 M. Here we show that the cyclin B2 promoter contains a CpG island and that 5-aza-deoxycytidine treatment leads to deregulation of cell cycle-dependent mRNA expression from this gene via a loss of repression in G0. Furthermore deletion of the DNA methyltransferase genes DNMT1 and DNMT3b leads to an increase in transcription of cyclin B2. Additionally DNA methylation .

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