Intergenerational Transfer of Epigenetic Information in Sperm

Abstract

The inheritance of information beyond DNA sequence, known as epigenetic inheritance, has been implicated in a multitude of biological processes from control of plant flowering time to cancer in humans. In addition to epigenetic inheritance that occurs in dividing cells of a multicellular organism, it is also increasingly clear that at least some epigenetic information is transmitted via the gametes in a multitude of organisms, including mammals. Here, I review the evidence for epigenetic information carriers in mammalian sperm, and explore the emerging field of intergenerational transfer of environmental information.

Figure 1.

Model for epigenetic events occurring immediately after fertilization. Schema shows the maternal genome (left) and paternal genome (right). The maternal genome is maintained in chromatin, whereas the paternal genome is primarily packaged into protamines, with a small fraction of genomic regions remaining associated with histones. After fertilization, binding of Stella to H3K9me2 protects underlying genomic regions from Tet3, which converts methylcytosine to hydroxymethylcytosine. Regions subject to hydroxymethylation are then passively demethylated during replication, resulting in near-global erasure of paternal cytosine methylation patterns. The maternal genome and a small fraction of the paternal genome are protected from this initial demethylation event because of their association with H3K9me2-marked histones.