Epigenetic reprogramming is necessary in somatic cell nuclear transfer (SCNT) embryos in order to erase the differentiation-associated epigenetic marks of donor cells. However, such epigenetic memories often persist throughout the course of clonal development, thus decreasing the cloning efficiency. Here, we explored reprogramming-refractory regions in bovine SCNT blastocyst transcriptomes. We observed that histone genes residing in the 1.5 Mb-spanning cow HIST1 cluster were coordinately downregulated in SCNT blastocysts. In contrast, both the non-histone genes of this cluster, and histone genes elsewhere remained unaffected. This indicated that the downregulation was specific to the HIST1 histone genes. We found that, after trichostatin A treatment, the HIST1 histone genes were de-repressed, and DNA methylation at their promoters was decreased to the level of IVF embryos. Therefore, our results indicate that the reduced expression of the HIST1 histone genes is a consequence of poor epigenetic reprogramming in SCNT blastocysts.
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