Non-Mendelian epigenetic heredity: gametic RNAs as epigenetic regulators and transgenerational signals.

Inheritance of epigenetic variations may account for a significant part of heritability in human and in mammalian models. Heritable epigenetic variations were reported in plants under the name 'paramutation' more than 50 years ago. Reports by E. Whitelaw and her colleagues and by our laboratory now describe a variety of situations resulting in epigenetic inheritance in mouse systems. In the three cases that we have analysed, a transcriptional increase is initiated by RNAs related to the locus, either microRNAs or transcript fragments. RNAs carried by the spermatozoon appear as the transgenerational signals responsible for paternal transmission. Extension from mouse models to human heredity, obviously speculative at present, is encouraged by the high load of RNA in human sperm.