Coordinated change of a ratio of methylated H3-Iysine 4 or acetylated H3 to acetylated H4 and DNA methylation is associated with tissue-specific gene expression in cloned pig

Abstract

Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3-lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.

Histone deacetylase inhibitor activity in royal jelly might facilitate caste switching in bees

“…To establish that 10HDA functions broadly and that the reactivation of Fas expression is not idiosyncratic to the NIH 3T3 K‐ras cell reporter system, we tested 10HDA in a second epigenetic reporter system, which is based on the reactivation of a silenced green fluorescent protein (GFP) locus (supplementary Fig S1B online). This ear fibroblast cell line (GF2–4) harbours a GFP gene that is heavily CpG methylated, as determined by bisulphite genomic sequencing (Kang et al , 2007). Treatment of GF2–4 cells with 5‐Aza results in the reactivation of the GFP locus (Kang et al , 2007).…”

“…This ear fibroblast cell line (GF2–4) harbours a GFP gene that is heavily CpG methylated, as determined by bisulphite genomic sequencing (Kang et al , 2007). Treatment of GF2–4 cells with 5‐Aza results in the reactivation of the GFP locus (Kang et al , 2007). Furthermore, a synergistic effect of a DNA demethylating agent and an HDACi on the expression of GFP was reported.…”

The functional role of the CARM1-SNF5 complex and its associated HMT activity in transcriptional activation by thyroid hormone receptor

“…Histone methylation is known to be stable metabolically (Waterborg, 1993;Kang et al, 2007). The presence of K9 methylated H3 (mH3-K9) in genes repressed by unliganded TR raises question as to how a liganded receptor overcomes this repressive activity during T3-dependent activation.…”

The influence of DNA sequence on epigenome-induced pathologies

“…The inheritance of epitypes between dividing somatic cells, such as the transmission of a histone PTM [46], is undoubtedly essential to tissue and organ development [47-49] and may be subject to various environmental influences that reveal a phenotype [50]; however, inheritance among somatic cells need not contribute causally to epigenetic inheritance across organismal generations. Again, we are interested herein in identifying epitypes that may be the primary cause of transgenerationally inherited epigenetic risk of acquiring a disease phenotype.…”