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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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Cooperative binding of the combined tandem Tudor–PHD domain of Uhrf2. A: Histone H3 N-terminal tail binding specificity of the TTD of Uhrf2 and of the combined TTD and PHD domain (TTD–PHD) of Uhrf1 and Uhrf2. Shown are means ± SEM from at least six independent experiments. B: Histone H3K9me3 binding of the combined TTD–PHD domains of Uhrf1 and Uhrf2, hybrid proteins (L1 and L2 specify inserted linker sequences derived from Uhrf1 and Uhrf2, respectively) and a stretch deletion Uhrf2 construct. Shown are means ± SEM from at least three independent experiments.
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fig04: Cooperative binding of the combined tandem Tudor–PHD domain of Uhrf2. A: Histone H3 N-terminal tail binding specificity of the TTD of Uhrf2 and of the combined TTD and PHD domain (TTD–PHD) of Uhrf1 and Uhrf2. Shown are means ± SEM from at least six independent experiments. B: Histone H3K9me3 binding of the combined TTD–PHD domains of Uhrf1 and Uhrf2, hybrid proteins (L1 and L2 specify inserted linker sequences derived from Uhrf1 and Uhrf2, respectively) and a stretch deletion Uhrf2 construct. Shown are means ± SEM from at least three independent experiments.

Mentions: Recently, several studies showed multivalent binding to histone-tail peptides [Ruthenburg et al., 2007]. In case of Uhrf1 and Uhrf2, the TTD is followed by a second histone-tail binding domain, a PHD domain (Fig. 1A). As the isolated PHD domains of Uhrf1 and Uhrf2 did not show binding to H3 histone-tail peptides (Fig. 2B) [Rottach et al., 2010], we tested whether the combination of the PHD and the TTD results in cooperative histone-tail binding. Surprisingly, the combined TTD–PHD domain of Uhrf2 displayed a fourfold increased binding to H3K9me2/me3 in comparison to the single TTD, which was not observed for the corresponding construct of Uhrf1 (Figs. .2B and 4A).


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)

Cooperative binding of the combined tandem Tudor–PHD domain of Uhrf2. A: Histone H3 N-terminal tail binding specificity of the TTD of Uhrf2 and of the combined TTD and PHD domain (TTD–PHD) of Uhrf1 and Uhrf2. Shown are means ± SEM from at least six independent experiments. B: Histone H3K9me3 binding of the combined TTD–PHD domains of Uhrf1 and Uhrf2, hybrid proteins (L1 and L2 specify inserted linker sequences derived from Uhrf1 and Uhrf2, respectively) and a stretch deletion Uhrf2 construct. Shown are means ± SEM from at least three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: Cooperative binding of the combined tandem Tudor–PHD domain of Uhrf2. A: Histone H3 N-terminal tail binding specificity of the TTD of Uhrf2 and of the combined TTD and PHD domain (TTD–PHD) of Uhrf1 and Uhrf2. Shown are means ± SEM from at least six independent experiments. B: Histone H3K9me3 binding of the combined TTD–PHD domains of Uhrf1 and Uhrf2, hybrid proteins (L1 and L2 specify inserted linker sequences derived from Uhrf1 and Uhrf2, respectively) and a stretch deletion Uhrf2 construct. Shown are means ± SEM from at least three independent experiments.
Mentions: Recently, several studies showed multivalent binding to histone-tail peptides [Ruthenburg et al., 2007]. In case of Uhrf1 and Uhrf2, the TTD is followed by a second histone-tail binding domain, a PHD domain (Fig. 1A). As the isolated PHD domains of Uhrf1 and Uhrf2 did not show binding to H3 histone-tail peptides (Fig. 2B) [Rottach et al., 2010], we tested whether the combination of the PHD and the TTD results in cooperative histone-tail binding. Surprisingly, the combined TTD–PHD domain of Uhrf2 displayed a fourfold increased binding to H3K9me2/me3 in comparison to the single TTD, which was not observed for the corresponding construct of Uhrf1 (Figs. .2B and 4A).

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