The third barrier to transgenerational inheritance in animals: somatic epigenetic resetting.

After early controversy, it is now increasingly clear that acquired responses to environmental factors may perpetuate across multiple generations-a phenomenon termed transgenerational epigenetic inheritance (TEI). Experiments with Caenorhabditis elegans, which exhibits robust heritable epigenetic effects, demonstrated small RNAs as key factors of TEI. Here, we discuss three major barriers to TEI in animals, two of which, the "Weismann barrier" and germline epigenetic reprogramming, have been known for decades. These are thought to effectively prevent TEI in mammals but not to the same extent in C. elegans. We argue that a third barrier-that we termed "somatic epigenetic resetting"-may further inhibit TEI and, unlike the other two, restricts TEI in C. elegans as well. While epigenetic information can overcome the Weismann barrier and transmit from the soma to the germline, it usually cannot "travel back" directly from the germline to the soma in subsequent generations. Nevertheless, heritable germline memory may still influence the animal's physiology by indirectly modifying gene expression in somatic tissues.