Epigenetic control of transgene expression and imprinting by genotype-specific modifiers.
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.
Allen
N D
ND
Department of Molecular Embryology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, England.
Norris
M L
ML
Surani
M A
MA
D000818:Animals; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic / Q000196:embryology / Q000235:genetics*; D010641:Phenotype; D001616:beta-Galactosidase / Q000096:biosynthesis
D004247:DNA; D001616:beta-Galactosidase