Hypomethylation of DNA during differentiation of friend erythroleukemia cells

Christman, J. K.; Weich, Nadine; Schoenbrun, B; Schneiderman, Natalie; Acs, George

doi:10.1083/jcb.86.2.366

Cited by 147 publications

(49 citation statements)

References 31 publications

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“…As shown in Fig. 1A, TfR1 message levels increased ϳ5-fold after 0.1 M 5-azaCdR treatment, similar to the effects of DMSO, a known inducer of MEL cell differentiation (28). A higher concentration of 5-aza-CdR further stimulated TfR1 mRNA expression (ϳ8-fold over the control).…”

Section: -Aza-cdr Treatment Alters Iron Homeostasis and Intracellulasupporting

confidence: 50%

5-Aza-2′-deoxycytidine Activates Iron Uptake and Heme Biosynthesis by Increasing c-Myc Nuclear Localization and Binding to the E-boxes of Transferrin Receptor 1 (TfR1) and Ferrochelatase (Fech) Genes

Ning

Liu

et al. 2011

Journal of Biological Chemistry

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The hypomethylating agent 5-aza-2-deoxycytidine (5-aza-CdR) and its derivatives have been successfully used for the treatment of myelodysplastic syndromes, and they frequently improve the anemia that usually accompanies these disorders. However, the molecular mechanisms underlying this action remain poorly understood. In this study, we used two erythroid models, murine erythroid leukemia cells and erythroid burst-forming unit-derived erythroblasts, to show that 5-aza-CdR induced erythroid differentiation and increased the expression of transferrin receptor 1 (TfR1) and ferrochelatase (Fech), thereby increasing iron uptake and heme biosynthesis. We have identified new regulatory E-boxes that lie outside of CpG islands in the TfR1 and Fech promoters, and the methylation status of these sites can be altered by 5-aza-CdR treatment. This in turn altered the binding of the transcription factor c-Myc to these promoter elements. Furthermore, 5-aza-CdR promoted the nuclear translocation of c-Myc and its binding to Max to form functional complexes. The coordinated actions of 5-aza-CdR on the methylation status of the target genes and in stimulating the nuclear translocation of c-Myc provide new molecular insights into the regulation of E-boxes and explain, at least in part, the increased erythroid response to 5-aza-CdR treatment.

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Section: -Aza-cdr Treatment Alters Iron Homeostasis and Intracellulasupporting

confidence: 50%

5-Aza-2′-deoxycytidine Activates Iron Uptake and Heme Biosynthesis by Increasing c-Myc Nuclear Localization and Binding to the E-boxes of Transferrin Receptor 1 (TfR1) and Ferrochelatase (Fech) Genes

Ning

Liu

et al. 2011

Journal of Biological Chemistry

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“…The mechanisms, however, by which polar compounds modulate cellular differentiation have not as yet been conclusively defined. NaBut has been shown to alter gene transcription by hyperacetylation of histones (Candido , 1978) or by interfering with DNA methylation (Christman et al, 1980). Nevertheless, it is not yet known whether all the polar compounds exclusively act at the nuclear site altering gene transcription or epigenetically affect other cellular functions and structures such as glutathione metabolism (Bill et al, 1988) or cell membranes (Blau & Epstein, 1979;Meilhoc et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous response to differentiation induction with different polar compounds in a clonal rat rhabdomyosarcoma cell line (BA-HAN-1C)

Gerharz

He²,

Engers³

et al. 1989

Br J Cancer

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SummaryThe clonal rat rhabdomyosarcoma cell line BA-HAN-IC was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotubelike giant cells. Exposure of BA-HAN-IC cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P<0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatine kinase activity used as a biochemical marker of differentiation (P<0.05) and the number of terminally differentiated myotube-like giant cells (P <0.001). Furthermore, about 5% of the mononuclear cells exhibited thick and thin myofilaments which were never observed in the mononuclear cells of the control. In contrast, the effects of DMSO, HMBA and NaBut were exclusively confined to a significant increase in biochemical differentiation (P<0.05), whereas no increase in morphological differentiation was observed and the number of myotube-like giant cells even significantly (P<0.001) decreased. This heterogeneous response to differentiation induction with different polar compounds probably indicates different mechanisms of action and suggests that the induction of biochemical differentiation might be independently regulated from events leading to cell fusion and terminal differentiation.

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“…It is also noteworthy that treatment of murine erythroleukemia cells with DMSO causes a decrease in DNA methylation (Christman et al 1980).…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of 5-azacytidine and .GAMMA.-interferon or dimethyl sulfoxide on expression of HLA class I antigens by PLC-PRF-5 cells.

Fukusato

Mohamad

Gerber

et al. 1988

Tohoku J. Exp. Med.

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Effect of 5-Azacytidine and y-Interferon or Dimethyl Sulfoxide on Expression of HLA Class I Antigens by PLC-PRF-5 Cells. Tohoku J. exp. Med., 1988, 155 (2), 117-128 In order to elucidate the mechanism by which HLA antigens expression is induced or enhanced on the injuried or transformed hepatocytes, we have made in vitro studies using human hepatic tumor-derived cell lines as a model system. In the present study, PLC-PRF-5 cells that have the integrated form of hepatitis B virus genome in DNA were treated with 5-azacytidine (5-azaC) in combination with y-interferon (IFN-y) or dimethyl sulfoxide (DMSO). HLA antigens on the cell surface were quantitated by using a modified cell-ELISA method. As a result, it was demonstrated that DMSO-or IFN-y-treatment enhanced expression of HLA class I antigens on the cell surface. In addition, enhanced expression of the antigens on PLC-PRF-5 cells treated with 5-azaC in combination with IFN-y or DMSO represented a synergistic effect of these inducers on HLA class I antigens expression although no changes in HLA antigens expression were induced after 5-azaC-treatment alone in short-term experiments. Furthermore, an indirect immunofluorescent analysis of hepatitis B surface antigen on the cells demonstrated increased expression of the antigen after 5-azaC-treatment alone. HLA class II antigens and hepatitis B core antigen were not induced even after those treatments and also not after a long-term experiment. These results might indicate possible modulation of HLA class I and hepatitis B virus antigens expression on the cultured cells by a DNA hypomethylating agent, 5-azaC. 5-azacytidine ; y-interferon ; dimethyl sulfoxide ; HLA antigens ; hepatitis B virus infection

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Hypomethylation of DNA during differentiation of friend erythroleukemia cells

Cited by 147 publications

References 31 publications

5-Aza-2′-deoxycytidine Activates Iron Uptake and Heme Biosynthesis by Increasing c-Myc Nuclear Localization and Binding to the E-boxes of Transferrin Receptor 1 (TfR1) and Ferrochelatase (Fech) Genes

5-Aza-2′-deoxycytidine Activates Iron Uptake and Heme Biosynthesis by Increasing c-Myc Nuclear Localization and Binding to the E-boxes of Transferrin Receptor 1 (TfR1) and Ferrochelatase (Fech) Genes

Heterogeneous response to differentiation induction with different polar compounds in a clonal rat rhabdomyosarcoma cell line (BA-HAN-1C)

Synergistic effect of 5-azacytidine and .GAMMA.-interferon or dimethyl sulfoxide on expression of HLA class I antigens by PLC-PRF-5 cells.

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