Relationship Between Transient DNA Hypomethylation and Erythroid Differentiation of Murine Erythroleukemia Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1988 Dec 1

PMID 3194403

Citations 10

Authors

A Razin

A Levine

T Kafri

S Agostini

T Gomi

G L CANTONI

Affiliations

Soon will be listed here.

Abstract

The state of DNA methylation in mouse erythroleukemia (MEL) cells has been analyzed in relation to commitment to differentiation in response to treatment with hexamethylenebisacetamide (HMBA). Previous experiments have shown that induction by HMBA involves transient genome-wide hypomethylation of DNA that is achieved by replacement of 5-methylcytosine with cytosine residues. The experiments described in the present communication revealed that hypomethylation is a very early event in the process of differentiation. Exposure of the cells to 3-deazaadenosine, an adenosine analog, in combination with homocysteine, resulted in the intracellular accumulation of 3-deazaadenosylhomocysteine, which caused an inhibition of HMBA-induced hypomethylation that was correlated with a comparable inhibition of differentiation. While these experiments suggest that hypomethylation is a necessary step in the process of differentiation, other experiments reported here indicate that hypomethylation of DNA may be necessary but not sufficient to trigger the whole program of differentiation in MEL cells. We found, for example that exposure of the cells to cycloheximide during the first 24 hr of induction by HMBA resulted in complete inhibition of differentiation without significant effect on the HMBA-induced hypomethylation. This result also indicates that the enzymatic machinery required for the hypomethylation of DNA is present in uninduced cells.

Citing Articles

DNA methylation dynamics of genomic imprinting in mouse development.

SanMiguel J, Bartolomei M Biol Reprod. 2018; 99(1):252-262.

PMID: 29462489 PMC: 6044325. DOI: 10.1093/biolre/ioy036.

Epigenetics in atherosclerosis and inflammation.

Wierda R, Geutskens S, Jukema J, Quax P, van den Elsen P J Cell Mol Med. 2010; 14(6A):1225-40.

PMID: 20132414 PMC: 3828841. DOI: 10.1111/j.1582-4934.2010.01022.x.

Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver.

Brunner A, Johnson D, Kim S, Valouev A, Reddy T, Neff N Genome Res. 2009; 19(6):1044-56.

PMID: 19273619 PMC: 2694474. DOI: 10.1101/gr.088773.108.

Acetylation-induced transcription is required for active DNA demethylation in methylation-silenced genes.

DAlessio A, Weaver I, Szyf M Mol Cell Biol. 2007; 27(21):7462-74.

PMID: 17709385 PMC: 2169050. DOI: 10.1128/MCB.01120-07.

Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells.

Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee P Genes Dev. 2007; 21(9):1050-63.

PMID: 17437993 PMC: 1855231. DOI: 10.1101/gad.1524107.

References

Reuben R, Wife R, Breslow R, Rifkind R, Marks P . A new group of potent inducers of differentiation in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1976; 73(3):862-6. PMC: 336019. DOI: 10.1073/pnas.73.3.862. View

Watanabe T, Oishi M . Dimethyl sulfoxide-inducible cytoplasmic factor involved in erythroid differentiation in mouse erythroleukemia (Friend) cells. Proc Natl Acad Sci U S A. 1987; 84(18):6481-5. PMC: 299101. DOI: 10.1073/pnas.84.18.6481. View

Singer J, STELLWAGEN R, Riggs A . 5-Methylcytosine content of rat hepatoma DNA substituted with bromodeoxyuridine. J Biol Chem. 1977; 252(15):5509-13. View

Chiang P, RICHARDS H, CANTONI G . S-Adenosyl-L-homocysteine hydrolase: analogues of S-adenosyl-L-homocysteine as potential inhibitors. Mol Pharmacol. 1977; 13(5):939-47. View

Gruenbaum Y, Stein R, Cedar H, Razin A . Methylation of CpG sequences in eukaryotic DNA. FEBS Lett. 1981; 124(1):67-71. DOI: 10.1016/0014-5793(81)80055-5. View

Aksamit R, Falk W, CANTONI G . Inhibition of chemotaxis by S-3-deazaadenosylhomocysteine in a mouse macrophage cell line. J Biol Chem. 1982; 257(2):621-5. View

Sheffery M, Marks P, Rifkind R . Gene expression in murine erythroleukemia cells. Transcriptional control and chromatin structure of the alpha 1-globin gene. J Mol Biol. 1984; 172(4):417-36. DOI: 10.1016/s0022-2836(84)80015-7. View

Salditt-Georgieff M, Sheffery M, Krauter K, Darnell Jr J, Rifkind R, Marks P . Induced transcription of the mouse beta-globin transcription unit in erythroleukemia cells. Time-course of induction and of changes in chromatin structure. J Mol Biol. 1984; 172(4):437-50. DOI: 10.1016/s0022-2836(84)80016-9. View

Scarpa S, Strom R, Bozzi A, Aksamit R, Backlund Jr P, Chen J . Differentiation of myoblast cell lines and biological methylation: 3-deazaadenosine stimulates formation of multinucleated myofibers. Proc Natl Acad Sci U S A. 1984; 81(10):3064-8. PMC: 345221. DOI: 10.1073/pnas.81.10.3064. View

10.

Razin A, Szyf M . DNA methylation patterns. Formation and function. Biochim Biophys Acta. 1984; 782(4):331-42. DOI: 10.1016/0167-4781(84)90043-5. View

11.

Sherman M, Shafman T, Spriggs D, Kufe D . Inhibition of murine erythroleukemia cell differentiation by 3-deazaadenosine. Cancer Res. 1985; 45(11 Pt 2):5830-4. View

12.

Razin A, Feldmesser E, Kafri T, Szyf M . Cell specific DNA methylation patterns; formation and a nucleosome locking model for their function. Prog Clin Biol Res. 1985; 198:239-53. View

13.

Nomura S, Yamagoe S, Kamiya T, Oishi M . An intracellular factor that induces erythroid differentiation in mouse erythroleukemia (Friend) cells. Cell. 1986; 44(4):663-9. DOI: 10.1016/0092-8674(86)90275-8. View

14.

Razin A, Szyf M, Kafri T, Roll M, Giloh H, Scarpa S . Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc Natl Acad Sci U S A. 1986; 83(9):2827-31. PMC: 323399. DOI: 10.1073/pnas.83.9.2827. View

15.

Marks P, Sheffery M, Rifkind R . Induction of transformed cells to terminal differentiation and the modulation of gene expression. Cancer Res. 1987; 47(3):659-66. View

16.

Fibach E, Reuben R, Rifkind R, Marks P . Effect of hexamethylene bisacetamide on the commitment to differentiation of murine erythroleukemia cells. Cancer Res. 1977; 37(2):440-4. View