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Cooperative DNA and histone binding by Uhrf2 links the two major repressive epigenetic pathways.

Pichler G, Wolf P, Schmidt CS, Meilinger D, Schneider K, Frauer C, Fellinger K, Rottach A, Leonhardt H - J. Cell. Biochem. (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Maximilians University Munich, Department of Biology II and Center for Integrated Protein Science Munich, Großhaderner Str. 2, 82152 Planegg-Martinsried, Germany.

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Opposite expression pattern of uhrf1 and uhrf2 during differentiation. A: Schematic outline of the multi-domain architecture of Uhrf1 in comparison to Uhrf2. An N-terminal ubiquitin-like domain (Ubl) is followed by a tandem Tudor domain (TTD), a plant homeodomain (PHD), a SET and RING associated (SRA) domain and a C-terminal really interesting new gene (RING) domain. Numbers indicate primary sequence similarities of single domains determined by BlastP search [Altschul, 1991]. Expression analysis of uhrf1 and uhrf2 by Real-time PCR in ESCs and somatic cells (B), during differentiation of wt J1 ESCs (C) and in various adult mouse tissues in comparison to the expression data in ESCs (D). Expression levels are relative to uhrf1 in wtJM8A (B), day 0 of differentiation (C) and to kidney (D) (uhrf1 set to 1). Shown are means ± SD of at least two independent experiments.
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fig01: Opposite expression pattern of uhrf1 and uhrf2 during differentiation. A: Schematic outline of the multi-domain architecture of Uhrf1 in comparison to Uhrf2. An N-terminal ubiquitin-like domain (Ubl) is followed by a tandem Tudor domain (TTD), a plant homeodomain (PHD), a SET and RING associated (SRA) domain and a C-terminal really interesting new gene (RING) domain. Numbers indicate primary sequence similarities of single domains determined by BlastP search [Altschul, 1991]. Expression analysis of uhrf1 and uhrf2 by Real-time PCR in ESCs and somatic cells (B), during differentiation of wt J1 ESCs (C) and in various adult mouse tissues in comparison to the expression data in ESCs (D). Expression levels are relative to uhrf1 in wtJM8A (B), day 0 of differentiation (C) and to kidney (D) (uhrf1 set to 1). Shown are means ± SD of at least two independent experiments.

Mentions: Recently, Uhrf1 has emerged as an essential factor for the maintenance of DNA methylation. Sequence analyses revealed that Uhrf2 harbors five recognizable domains similar to Uhrf1 (Fig. 1A), but its role in the regulation of DNA methylation is still unclear. We compared the expression pattern of uhrf1 and uhrf2 in ESCs and somatic cells, during differentiation and in differentiated mouse tissues (Fig. 1B–D and Supplementary Fig. S1). Interestingly, both genes show opposite expression patterns; while uhrf1 is expressed in ESCs and down regulated during differentiation, which is consistent with previous reports [Muto et al., 1995; Fujimori et al., 1998; Hopfner et al., 2000], uhrf2 is upregulated and highly expressed in differentiated mouse tissues. The switch in the expression pattern argues against a functional redundancy of both genes and is consistent with the drastic loss of DNA methylation in uhrf1−/− ESCs despite the presence of intact uhrf2 alleles. Therefore, the opposite expression pattern of both genes suggests different functional roles of uhrf1 and uhrf2 in development.


Cooperative DNA and histone binding by Uhrf2 links the two major repressive epigenetic pathways.

Pichler G, Wolf P, Schmidt CS, Meilinger D, Schneider K, Frauer C, Fellinger K, Rottach A, Leonhardt H - J. Cell. Biochem. (2011)

Opposite expression pattern of uhrf1 and uhrf2 during differentiation. A: Schematic outline of the multi-domain architecture of Uhrf1 in comparison to Uhrf2. An N-terminal ubiquitin-like domain (Ubl) is followed by a tandem Tudor domain (TTD), a plant homeodomain (PHD), a SET and RING associated (SRA) domain and a C-terminal really interesting new gene (RING) domain. Numbers indicate primary sequence similarities of single domains determined by BlastP search [Altschul, 1991]. Expression analysis of uhrf1 and uhrf2 by Real-time PCR in ESCs and somatic cells (B), during differentiation of wt J1 ESCs (C) and in various adult mouse tissues in comparison to the expression data in ESCs (D). Expression levels are relative to uhrf1 in wtJM8A (B), day 0 of differentiation (C) and to kidney (D) (uhrf1 set to 1). Shown are means ± SD of at least two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569875&req=5

fig01: Opposite expression pattern of uhrf1 and uhrf2 during differentiation. A: Schematic outline of the multi-domain architecture of Uhrf1 in comparison to Uhrf2. An N-terminal ubiquitin-like domain (Ubl) is followed by a tandem Tudor domain (TTD), a plant homeodomain (PHD), a SET and RING associated (SRA) domain and a C-terminal really interesting new gene (RING) domain. Numbers indicate primary sequence similarities of single domains determined by BlastP search [Altschul, 1991]. Expression analysis of uhrf1 and uhrf2 by Real-time PCR in ESCs and somatic cells (B), during differentiation of wt J1 ESCs (C) and in various adult mouse tissues in comparison to the expression data in ESCs (D). Expression levels are relative to uhrf1 in wtJM8A (B), day 0 of differentiation (C) and to kidney (D) (uhrf1 set to 1). Shown are means ± SD of at least two independent experiments.
Mentions: Recently, Uhrf1 has emerged as an essential factor for the maintenance of DNA methylation. Sequence analyses revealed that Uhrf2 harbors five recognizable domains similar to Uhrf1 (Fig. 1A), but its role in the regulation of DNA methylation is still unclear. We compared the expression pattern of uhrf1 and uhrf2 in ESCs and somatic cells, during differentiation and in differentiated mouse tissues (Fig. 1B–D and Supplementary Fig. S1). Interestingly, both genes show opposite expression patterns; while uhrf1 is expressed in ESCs and down regulated during differentiation, which is consistent with previous reports [Muto et al., 1995; Fujimori et al., 1998; Hopfner et al., 2000], uhrf2 is upregulated and highly expressed in differentiated mouse tissues. The switch in the expression pattern argues against a functional redundancy of both genes and is consistent with the drastic loss of DNA methylation in uhrf1−/− ESCs despite the presence of intact uhrf2 alleles. Therefore, the opposite expression pattern of both genes suggests different functional roles of uhrf1 and uhrf2 in development.

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.

View Article: PubMed Central - PubMed

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