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DNA methylation, retroviruses, and embryogenesis
Author(s) -
Jaenisch Rudolf,
Harbers Klaus,
Jähner Detlev,
Stewart Colin,
Stuhlmann Heidi
Publication year - 1982
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240200403
Subject(s) - biology , embryo , embryonal carcinoma , microbiology and biotechnology , virus , genome , virology , transfection , dna methylation , murine leukemia virus , cellular differentiation , cell culture , gene , genetics , gene expression
By exposing preimplantation embryos to Moloney leukemia virus (M‐MuLV), we have previously derived substrains of mice designated as Mov‐1‐Mov‐13 which genetically transmit the virus from one generation to the next. In some of the substrains the inserted viral genome becomes activated at specific stages of embryogenesis and the available evidence suggests that these viral genomes are developmentally regulated. To investigate the effect of cellular differentiation on virus expression, M‐MuLV was introduced either into preimplantation or postimplantation mouse embryos or into embryonal carcinoma (EC) cells. Whereas preimplantation embryos or EC cells are not permissive for virus expression, efficient replication occurred in postimplantation embryos or in differentiated cell lines. The viral genomes introduced into early embryonal cells were highly methylated and noninfcctious when analyzed in the adult. In contrast, viral genomes introduced into postimplantation embryos or into differentiated cells remained unmethylated and were infectious in a transfection assay. These results demonstrate an efficient de novo methylation activity which appears to be involved in repression of genes introduced into pluripotent embryonal cells and which is not observed in cells of the postimplantation embryo or in differentiated cells in tissue culture.