Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Genetics and Developmental Biology Unit, Institut Curie, INSERM U934, CNRS UMR3215, PSL University, Paris, France.
Essays Biochem. 2019 Dec 20;63(6):663-676. doi: 10.1042/EBC20190034.
Monoallelic gene expression occurs in diploid cells when only one of the two alleles of a gene is active. There are three main classes of genes that display monoallelic expression in mammalian genomes: (1) imprinted genes that are monoallelically expressed in a parent-of-origin dependent manner; (2) X-linked genes that undergo random X-chromosome inactivation in female cells; (3) random monoallelically expressed single and clustered genes located on autosomes. The heritability of monoallelic expression patterns during cell divisions implies that epigenetic mechanisms are involved in the cellular memory of these expression states. Among these, methylation of CpG sites on DNA is one of the best described modification to explain somatic inheritance. Here, we discuss the relevance of DNA methylation for the establishment and maintenance of monoallelic expression patterns among these three groups of genes, and how this is intrinsically linked to development and cellular states.
单等位基因表达发生在二倍体细胞中,此时基因的两个等位基因中只有一个是活跃的。在哺乳动物基因组中,有三类主要的基因表现出单等位基因表达:(1)印迹基因,以亲本来源依赖的方式单等位基因表达;(2)X 连锁基因,在雌性细胞中随机发生 X 染色体失活;(3)位于常染色体上的随机单等位基因表达的单个和簇状基因。在细胞分裂过程中单等位基因表达模式的遗传性暗示了表观遗传机制参与了这些表达状态的细胞记忆。其中,DNA 上 CpG 位点的甲基化是解释体细胞遗传的最佳描述修饰之一。在这里,我们讨论了 DNA 甲基化对于这三组基因中单等位基因表达模式的建立和维持的相关性,以及它如何与发育和细胞状态内在相关。