组蛋白 H4 赖氨酸 20 单甲基化由组蛋白甲基转移酶 SET8 介导，可激活 Wnt 靶基因。
Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation.
机构信息
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
出版信息
Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3116-23. doi: 10.1073/pnas.1009353108. Epub 2011 Jan 31.
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.
组蛋白甲基化在转录调控中具有重要作用。然而，与 H3K4 和 H3K9 甲基化不同，H4K20 单甲基化（H4K20me-1）在转录调控中的作用尚不清楚。在这里，我们发现 Wnt3a 通过组蛋白甲基转移酶 SET8 特异性地刺激 T 细胞因子（TCF）结合元件上的 H4K20 单甲基化。此外，SET8 对于哺乳动物细胞和斑马鱼中 Wnt 报告基因和靶基因的激活至关重要。此外，SET8 直接与淋巴增强因子-1（LEF1）/TCF4 相互作用，这种相互作用受 Wnt3a 调节。因此，我们得出结论，SET8 是 Wnt 信号转导介质，被 LEF1/TCF4 募集来调节 Wnt 激活基因的转录，可能是通过靶基因启动子上的 H4K20 单甲基化。我们的研究结果还表明，H4K20me-1 至少在经典 Wnt 信号通路中是基因转录激活的标志物。
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