EPIGENETIC CONTROL OF TRANSGENE EXPRESSION AND IMPRINTING BY GENOTYPE-SPECIFIC MODIFIERS
EPIGENETIC CONTROL OF TRANSGENE EXPRESSION AND IMPRINTING BY GENOTYPE-SPECIFIC MODIFIERS
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DOI：
10.1016/0092-8674(90)90195-k
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发表时间：
1990-06-01
期刊：
影响因子：
64.5
通讯作者：
SURANI, MA
中科院分区：
文献类型：
--
作者：
ALLEN, ND;NORRIS, ML;SURANI, MA
转基因位点TKZ751的表达和DNA甲基化由基因型特异性修饰基因控制。DBA/2和129基因背景增强了表达，而BALB/c基因背景抑制了表达，但仅在母系遗传了BALB/c修饰子之后。转基因位点的表观遗传修饰在连续几代中累积，在BALB/c小鼠中，连续三次种系传代后导致不可逆的甲基化。因此，在TKZ751位点，种系不能逆转先前获得的表观遗传修饰，这一过程通常是恢复基因组全能性所必需的。因此，基因型特异性修饰基因通过表观遗传修饰调控TKZ751基因座的外显率和表达性以及亲本印迹。
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.