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Snail also acts as a transactivator for the expression of tumor-associated cytokines

 

Snail has been known to repress transcription of target genes during epithelial-mesenchymal transition (EMT), a crucial mechanism of tumors metastasis. However, this zinc finger transcription factor was also found to act as an activator, recently. Hsu et al. demonstrated the underlying mechanism of Snail-mediated target gene transactivation, and also identified several target genes. The article was published on Cancer Cell.

 

Snail induces EMT by repressing transcription of CDH1 gene, which encoded cell adhesion protein E-cadherin. Mechanistically, Snail promotes transcriptional silencing by recruiting corepressors to the promoter of CDH1, meanwhile modifying the chromatin. Several corepressor complexes have been reported, including HDAC1/HDAC2/Sin3A, polycomb repressive complex and PRMT5. In this study, researchers found acetylation of Snail is important for its recruitment of different coregulators, which determine Snail as an activator or a repressor. CREB-binding protein (CBP) plays a critical role in Snail-mediated target gene transactivation by acetylating Snail to prevent the repressor complex formation. The ChIP results indicated that the activating and repressing effect of Snail may happened in the same cell, depends on Snail acetylation states. In addition, they identified several targets activated by Snail, including TNF-α, a important cytokine involved in acute inflammation, as well as CCL3 and CCL5, cytokines promote accumulation of tumor-associated macrophages. These findings broaden the view of Snail as a transcriptional activator for the expression of tumor-associated cytokines.

 

Reference:
Cancer Cell. 2014 Oct 13;26(4):534-48. 

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