Histone Mono-methylase SET8 is a Novel Regulator Modulating Canonical Wnt Target Gene Expression

来源 :Wnt信号、器官发育和干细胞国际学术大会(Wnt Signaling,Organogenesis,and Stem Ce | 被引量 : 0次 | 上传用户:nongfeng4
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  In canonical Wnt signaling pathway, many co-activators including histone modification enzymes are recruited into β-catenin/TCF-4 transcription complex at target gene promoters to facilitate gene transcription.Here we show that SET8 docks at TCFs binding element (TBE) of Wnt target genes, through interacting with TCF-4/LEF-1, and establishes the mono-methylation of H4K20 (H4K20me-l) as a marker for transcriptional activation.Wnt-3a could induce H4K20me-1 augment at TBE specifically, and its corresponding methyltransferase, SET8, is crucial for activation of Wnt reporter and target genes in mammalian cells.Consistently, morpholino (MO) of Set8 in zebrafish leads to kind of similar phenotype as Wnt8 morphants, and zSet8 MO greatly boosts zWnt8 phenotype, indicating the evolutionally conserved function of SET8 in Wnt signaling pathway.Furthermore, we reveal that SET8 could interact with TCF-4/LEF-I directly,and this interaction is regulated by Wnt-3a stimulation or β-catenin overexpression, suggesting the signaling triggered SET8 relocation on chromosome.
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