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Cancer Cell. 2016 Mar 14;29(3):354-366. doi: 10.1016/j.ccell.2016.01.013. Epub 2016 Feb 18.

Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development.

Author information

1
Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece; School of Medicine, University of Crete, 71003 Herakleion, Crete, Greece.
2
Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece.
3
Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece. Electronic address: talianidis@fleming.gr.

Abstract

Smyd3 is a protein methyltransferase implicated in cancer development. Here we show that Smyd3 expression in mice is required for chemically induced liver and colon cancer formation. In these organs Smyd3 functions in the nucleus, stimulating the transcription of several key regulators involved in cell proliferation, epithelial-mesenchymal transition, the JAK/Stat3 oncogenic pathway, as well as the Myc and Ctnnb1 oncogenes. Smyd3 interacts with H3K4Me3-modified histone tails, which facilitates its recruitment to the core promoter regions of most active genes. Smyd3 binding density on target genes positively correlates with increased RNA polymerase-II density and transcriptional outputs. Despite its widespread distribution, the transcription-potentiating function of Smyd3 is restricted to a particular set of genes, whose expression is induced specifically during carcinogenesis.

PMID:
26908355
DOI:
10.1016/j.ccell.2016.01.013
[Indexed for MEDLINE]
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