Jiang S, Hemann M A, Lee M P, Feinberg A P
Graduate Program in Cellular and Molecular Medicine, Graduate Program in Human Genetics, Department of Medicine, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, USA.
Genomics. 1998 Nov 1;53(3):395-9. doi: 10.1006/geno.1998.5511.
Genomic imprinting is an epigenetic modification of the gamete or zygote leading to parental origin-specific differential expression of the two alleles of a gene in somatic cells of the offspring. We previously reported that the human KVLQT1 gene is imprinted and disrupted in patients with germline balanced chromosomal rearrangements and Beckwith-Wiedemann syndrome. In human, the gene is imprinted in most fetal tissues except the heart, and KVLQT1 is part of a 1-Mb cluster of imprinted genes on human chromosome 11p15. 5. We sought to determine whether the mouse Kvlqt1 gene is imprinted, by performing interspecific crosses of 129/SvEv mice with CAST/Ei (Mus musculus castaneus). We identified a transcribed polymorphism that distinguishes the two parental alleles in F1 offspring. Examination of embryonic, neonatal, and postnatal tissues revealed that Kvlqt1 is imprinted in mouse early embryos, in both female 129 x male CS and female CS x male 129 offspring, with preferential expression of the maternal allele, like the human homologue. Surprisingly, imprinting was developmentally relaxed, and the developmental stage and tissue specificity of relaxation of imprinting was strain-dependent. To our knowledge, this is the first example of an endogenous gene that shows strain-dependent developmental relaxation of imprinting.
基因组印记是配子或受精卵的一种表观遗传修饰，导致后代体细胞中一个基因的两个等位基因呈现亲本来源特异性的差异表达。我们之前报道过，人类KVLQT1基因在患有生殖系平衡染色体重排和贝克威思-维德曼综合征的患者中发生印记缺失。在人类中，该基因在除心脏外的大多数胎儿组织中发生印记，并且KVLQT1是人类染色体11p15.5上一个1兆碱基印记基因簇的一部分。我们试图通过将129/SvEv小鼠与CAST/Ei（小家鼠栗色种）进行种间杂交，来确定小鼠Kvlqt1基因是否发生印记。我们鉴定出一种转录多态性，可区分F1后代中的两个亲本等位基因。对胚胎、新生和出生后组织的检查表明，Kvlqt1在小鼠早期胚胎中发生印记，在雌性129×雄性CS和雌性CS×雄性129的后代中均有印记，且母本等位基因优先表达，与人类同源基因情况类似。令人惊讶的是，印记在发育过程中出现松弛，且印记松弛的发育阶段和组织特异性具有品系依赖性。据我们所知，这是内源性基因呈现品系依赖性发育印记松弛的首个例子。
