Institute Medical Microbiology, University Zürich, Zurich, Switzerland.
Max Planck Institute of Molecular Genetics, Berlin, Germany.
J Physiol. 2024 Jun;602(11):2537-2545. doi: 10.1113/JP284424. Epub 2023 Sep 29.
Epigenetic modifications can alter the function of genes. The epigenetics changes are caused by environmental effects, which lead to chemical modifications of the DNA or the chromatin. The mechanisms involve the influence of small interfering siRNAs on gene silencing. Epigenetic changes normally last only during the life-time of an individual and are erased in embryos and eggs for a naive progeny. The genomes are reprogrammed and the chemical modifications removed to restart the next generation. However, there are mechanisms that allow the genome to escape from such a clearing effect so that modifications can be transmitted to one or more subsequent generations. In the germline of animal cells small RNAs, including piRNAs, have evolved which guarantee a higher degree of fidelity for transmission of genetic information, guarding especially against the detrimental effect caused by transposon activity. piRNA is essential for transposon silencing for survival of a species and protection of subsequent generations. Inactivation of piRNA results in abundant transposon activity and sperm infertility. The effect in humans has been described but is less distinct. Some stress-induced epigenetic changes are transitory in mice and can be reversed by a change of environment or lifestyle.
表观遗传修饰可以改变基因的功能。这些表观遗传变化是由环境影响引起的,导致 DNA 或染色质的化学修饰。其机制涉及小干扰 siRNA 对基因沉默的影响。通常,表观遗传变化仅在个体的生命周期内持续存在,并在胚胎和卵子中被抹去,以获得原始的后代。基因组会被重新编程,化学修饰被去除,以启动下一代。然而,存在一些机制可以使基因组逃脱这种清除效应,从而使修饰可以传递给一个或多个后续世代。在动物细胞的生殖系中,已经进化出包括 piRNA 在内的小 RNA,它们保证了遗传信息传递的更高保真度,特别是防止转座子活性造成的有害影响。piRNA 对于转座子沉默、物种生存和后代保护至关重要。piRNA 的失活会导致大量转座子的激活和精子不育。这一效应在人类中已经被描述,但不太明显。在小鼠中,一些应激诱导的表观遗传变化是短暂的,可以通过环境或生活方式的改变来逆转。