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Bromodomain and extra-terminal proteins are required in STAT5-mediated transcription

 

Signal transducer and activator of transcription 5 (STAT5) is a essential regulator for genes related to cell proliferation and survival, and is often upregulated in cancer. Previous study showed STAT5-mediated transcription can be inhibited by deacetylase inhibitor trichostatin A (TSA). However, the mechanism and factors involved in this process remain elusive. Pinz et al. found deacetylase inhibitors lead to the delocalization of the bromodomain and extra-terminal (BET) protein Brd2, as well as Brd2-related factor TBP to hyperacetylated chromatin, via the global upregulation of histone acetylation. The article was published in Nucleic Acids Research.

 

This result do not match the initial hypothesis that deacetylase inhibitors directly target STAT5 acetylation. BET inhibitor (+)-JQ1 suppressed STAT5 target gene expression, indicating a important role of BET in regulation of STAT5 activity. Using chromatin immunoprecipitation, researchers proved that BET protein Brd2 is associated with the Cis, STAT5 target gene, and is disassociated in the presence of TSA. The findings indicate that deacetylase inhibitors interfere STAT5-mediated transcription by inhibiting activity of Brd2, which is important for the proper recruitment of STAT5 target genes transcription.

 

Reference:
Nucleic Acids Res. 2015 Mar 13. pii: gkv188.

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