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Publication : Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation.

First Author  Li Z Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  8 Pages  3116-23
PubMed ID  21282610 Mgi Jnum  J:169069
Mgi Id  MGI:4939822 Doi  10.1073/pnas.1009353108
Citation  Li Z, et al. (2011) From the Cover: Feature Article: Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Proc Natl Acad Sci U S A 108(8):3116-23
abstractText  Histone methylation has an important role in transcriptional regulation. However, unlike H3K4 and H3K9 methylation, the role of H4K20 monomethylation (H4K20me-1) in transcriptional regulation remains unclear. Here, we show that Wnt3a specifically stimulates H4K20 monomethylation at the T cell factor (TCF)-binding element through the histone methylase SET8. Additionally, SET8 is crucial for activation of the Wnt reporter gene and target genes in both mammalian cells and zebrafish. Furthermore, SET8 interacts with lymphoid enhancing factor-1 (LEF1)/TCF4 directly, and this interaction is regulated by Wnt3a. Therefore, we conclude that SET8 is a Wnt signaling mediator and is recruited by LEF1/TCF4 to regulate the transcription of Wnt-activated genes, possibly through H4K20 monomethylation at the target gene promoters. Our findings also indicate that H4K20me-1 is a marker for gene transcription activation, at least in canonical Wnt signaling.
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