Epigenetic control of transgene expression and imprinting by genotype-specific modifiers

• Published in: Cell Vol. 61; no. 5; pp. 853 - 861
• Main Authors: Allen, Nicholas D., Norris, Michael L., Surani, M.Azim
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.06.1990; Cell Press
• Subjects: Animals; beta-Galactosidase - biosynthesis; Biological and medical sciences; DNA - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - genetics; Genotype; Methylation; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Transgenic - embryology; Mice, Transgenic - genetics; Molecular and cellular biology; Molecular genetics; Phenotype; Gel electrophoresis; Rodentia; Transgenic animal; Genotype; Gene expression; Vertebrata; Reversion; Mammalia; Gene; Mouse; DNA; Blotting assay; Epigenetics; Methylation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(90)90195-K

Expression and DNA methylation of the transgene locus TKZ751 are controlled by genotype-specific modifier genes. The DBA/2 and 129 genetic backgrounds enhanced expression, while the BALB/c background suppressed expression, but only following maternal inheritance of the BALB/c modifier. Epigenetic modification of the transgene locus was cumulative over successive generations, which in BALB/c mice resulted in an irreversible methylation after three consecutive germline passages. Therefore, at the TKZ751 locus the germline fails to reverse previously acquired epigenetic modifications, a process that is usually essential to restore the genomic totipotency. Hence the genotype-specific modifier genes regulate penetrance and expressivity as well as parental imprinting of the TKZ751 locus through epigenetic modification.