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Control of histone acetylation is a part of the epigenetic mechanism that regulates gene expression and chromatin architecture. The members of the bromodomain and extra terminal domain (BET) protein family are a group of epigenetic readers that recognize histone acetylation, whereas histone deacetyl- ases such as sirtuin 1 (SIRT1) function as epigenetic erasers. We observed that BET inhibition by the specific inhibitor JQ1 upregulated SIRT1 expression and activated SIRT1. Moreover, we observed that BET inhibition functionally reversed the pro-inflammatory effect of SIRT1 inhibition in a cellular lung disease model. SIRT1 activation is desirable in many age-related, metabolic and inflammatory diseases; our results suggest that BET protein inhibition would be beneficial in treatment of those conditions. Most importantly, our findings demonstrate a novel mechanism of SIRT1 activation by inhibition of the BET proteins.

Original publication

DOI

10.1002/cbic.201500272

Type

Journal article

Journal

Chembiochem

Publication Date

21/09/2015

Volume

16

Pages

1997 - 2001

Keywords

SIRT1, acetylation, bromodomain and extra terminal domain protein, cancer, epigenetics, gene expression, Animals, Azepines, Cell Line, Cell Line, Tumor, Epigenesis, Genetic, HEK293 Cells, Humans, Inflammation, MCF-7 Cells, Mice, Nuclear Proteins, Protein-Serine-Threonine Kinases, RNA Interference, RNA, Small Interfering, Sirtuin 1, Transcription Factors, Triazoles, Up-Regulation