Cooperative DNA and histone binding by Uhrf2 links the two major repressive epigenetic pathways.
Bottom Line: Besides the cooperative DNA and histone binding that is characteristic for Uhrf2, we also found an opposite expression pattern of uhrf1 and uhrf2 during differentiation.Ectopic expression of Uhrf2 in uhrf1(-/-) embryonic stem cells did not restore DNA methylation at major satellites indicating functional differences.We propose that the cooperative interplay of Uhrf2 domains may contribute to a tighter epigenetic control of gene expression in differentiated cells.
Affiliation: Ludwig Maximilians University Munich, Department of Biology II and Center for Integrated Protein Science Munich, Großhaderner Str. 2, 82152 Planegg-Martinsried, Germany.Show MeSH
Related in: MedlinePlus
Mentions: To investigate whether Uhrf1 and Uhrf2 are functionally redundant we performed interaction and rescue assays. Like Uhrf1, also Uhrf2 interacts with Dnmts (Supplementary Fig. S6) suggesting a similar function in DNA methylation. To test for such a functional role, we ectopically expressed Uhrf2-GFP or Uhrf1-GFP in uhrf1−/− ESCs and determined DNA methylation levels at major satellites by pyrosequencing. While ectopic expression of Uhrf1-GFP led to significant increase of DNA methylation levels at CpG sites of major satellite DNA in uhrf1−/− ESCs, Uhrf2-GFP did not restore DNA methylation at these sites (Fig. 5). These results point to functional differences between Uhrf1 and Uhrf2 in vivo.
Affiliation: Ludwig Maximilians University Munich, Department of Biology II and Center for Integrated Protein Science Munich, Großhaderner Str. 2, 82152 Planegg-Martinsried, Germany.