We asked if ancestral liver damage leads to heritable reprogramming of hepatic wound-healing. We discovered that male rats with a history of liver damage transmit epigenetic suppressive adaptation of the fibrogenic component of wound-healing through male F1 and F2 generations. Underlying this adaptation was reduced generation of liver myofibroblasts, increased hepatic expression of antifibrogenic PPAR-γ and decreased expression of profibrogenic TGF-β1. Remodelling of DNA methylation and histone acetylation underpinned these alterations in gene expression. Sperm from rats with liver fibrosis were enriched for H2A.Z and H3K27me3 at PPAR-γ chromatin. These sperm chromatin modifications were transmittable by adaptive serum transfer from fibrotic rats and were induced in stem cells exposed to myofibroblast-conditioned media. A myofibroblast secreted soluble factor therefore stimulates heritable epigenetic signatures to sperm so as to adapt fibrogenesis in offspring. Humans with mild liver fibrosis display PPAR-γ promoter hypomethylation compared with severe fibrotics, thus lending support for epigenetic regulation of fibrosis.

Blood-derived DNA methylation measurements may not always reflect methylation within other tissues. Further measurements of blood-derived and tissue-specific methylation patterns are warranted to understand the complexity of tissue-specific responses to altered nutritional exposure.

This is the first study reporting causal effects of maternal folate depletion on gene-specific methylation in fetal gut. These observations support reports that altered methyl donor intake during development affects DNA methylation in the offspring. The consequences of epigenetic changes for health throughout the life course remain to be investigated.

The above paper originally reported that H5N1 viruses are resistant to interferon in the SJPL cell line. The editors wish to alert our readers about three facts that may affect this conclusion. First, Ngunjiri et al. (Nat. Med. 18, 1456-1457, 2012 have recently found that aliquots of the SJPL cell line obtained from the American Type Culture Collection were heavily contaminated with mycoplasma. Although the mycoplasma status of the cells used in the original paper is unknown, it is not possible to rule out that they were contaminated. Second, SJPL cells were originally reported to be of porcine origin, but a recent analysis (Silversides, D.W. et al. J. Virol. 84, 5454-5455, 2010) has indicated that they are of simian origin. Third, Ngunjiri et al. have found H5N1 viruses to be sensitive to interferons in all cell lines tested from multiple species.Corrigendum: Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists In the version of this article initially published, the authors inadvertently used α-tubulin normalization data in the western blots shown in Figure 4b and Figure 4e from separate experiments used to generate the other bands shown. The error did not affect the main conclusions of the paper. Nonetheless, to verify the data, the authors have repeated the experiments, and the data from one such experiment are now included for both these figure panels. The authors regret the occurrence and apologize for it. The error has been corrected in the HTML and PDF versions of the article. In the version of this article initially published, in Figure 6f the left-hand graph was an inadvertent duplication of the right-hand graph. The error does not alter the overall conclusions of the paper. The figure has been corrected in the HTML and PDF versions of the article. 1592volume 18 | number 10 | october 2010 nature medicine a d d e n da a n d co r r i g e n da npg