Modifiers of epigenetic reprogramming show paternal effects in the mouse

Abstract

There is increasing evidence that epigenetic information can be inherited across generations in mammals, despite extensive reprogramming both in the gametes and in the early developing embryo. One corollary to this is that disrupting the establishment of epigenetic state in the gametes of a parent, as a result of heterozygosity for mutations in genes involved in reprogramming, could affect the phenotype of offspring that do not inherit the mutant allele. Here we show that such effects do occur following paternal inheritance in the mouse. We detected changes to transcription and chromosome ploidy in adult animals. Paternal effects of this type have not been reported previously in mammals and suggest that the untransmitted genotype of male parents can influence the phenotype of their offspring.

Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin

“…Although histone modifications in paternal chromatin could be one contributing route (Hammoud et al 2009, Brykczynska et al 2010, information 'embossed' into the differential packaging of sperm chromatin also offers potential non-Mendelian traits the chance to influence zygotic phenotype. Evidence for an epigenetic influence driving such variation has been presented for both human (Pembrey et al 2006, Jirtle & Skinner 2007 and animal inheritance (Chong et al 2007). We speculate that the underlying framework for post-translational modifications including histone methylation is established by differential packaging of sperm chromatin, which the limited MNase digestion used in this and our related study (Arpanahi et al 2009) both reveals and exploits.…”

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…Van der Heijden and his colleagues (2006) suggested that these histones, as well as methylated cytosines in centromeric DNA, are associated with the transgenerational maintenance of the structure of centromeric heterochromatin. Chong et al (2007) reported that when male mice had mutations in genes involved in epigenetic programming-in a gene that encodes a chromatin remodeler protein, and in another that encodes DNA methyltransferasethere were phenotypic effects on their offspring, even when they did not inherit the defective gene. Extensive epigenetic (methylation) variation has been found in human germ cells (Flanagan et al 2006), but whether and to what extent this variation is passed between generations is not known.…”

RNA regulation of epigenetic processes

“…(104) It has also been reported that modifiers of epigenetic reprogramming show paternal effects in mice. (111) Perhaps the most exciting aspect of this field, and one with the capacity to change our view of inheritance and evolution, (109) is the recently described phenomenon of 'paramutation'. Paramutation refers to the allele-specific transfer of epigenetic information to cause the heritable silencing of one allele by another and appears to involve RNA signalling in both maize and mice.…”