title: Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhenfei
authors.initials: Z
authors.lastname: Li
authors.forename: Fen
authors.initials: F
authors.lastname: Nie
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D015415:Biomarkers; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008322:Mammals; D008745:Methylation; D015398:Signal Transduction / Q000235:genetics; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000235:genetics*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015415:Biomarkers; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D051821:Lymphoid Enhancer-Binding Factor 1; D008239:Lysine; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D029961:Zebrafish Proteins; C507321:LEF1 protein, zebrafish; C497574:Lef1 protein, mouse; C090743:Tcf4 protein, mouse; C517154:Tcf4 protein, zebrafish; C555510:WNT3A protein, human; C555511:Wnt3a protein, mouse; C470730:KMT5A protein, human; C529566:KMT5a protein, mouse