Novel Epigenetic Regulatory Mechanism in Wnt Signaling Uncovered
Source:
Time: 2011-02-12
A team of researchers led by LI Lin at Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, found that histone H4 Lys20 monomethylase SET8 could participate in canonical Wnt signaling to activate target gene expression.
Histone methylation function in Wnt signaling has attracted more and more attentions and histone H4 Lys20 mono-methylation (H4K20me-1) has been linked to transcription repression. In this work, LI Zhenfei and colleagues found that SET8 mediated H4K20me-1 accumulated at the promoter of Wnt target genes upon Wnt stimulation. This modification showed a dynamic alteration just like transcription activator -catenin, indicating its positive role in gene transcription. Furthermore, SET8 activated Wnt target gene expression in both mammalian cells and zebrafish embryos. Besides, SET8 could synergistically regulate Wnt target gene expression to affect embryonic development of zebrafish together with Wnt8. And then, this group further found that TCF4 recruited SET8 to Wnt target gene promoters and Wnt/catenin could facilitate interaction between SET8 and TCF4 by expelling Groucho from TCF4. These findings provide a picture of how SET8 responds to Wnt signaling, accumulates at the promoter of target genes, and establishes H4K20me-1 as a transcription activation marker.
This work entitled ‘Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation’ was published in PNAS on January 31, 2011. This work was supported grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality. (SIBCB)
AUTHOR CONTACT:
LI Lin
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
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