Profiling the regulatory interplay of BET bromodomains and Sirtuins in cancer cell lines

Abstract

Alterations in epigenetic marking, due to changes in expression or activity of epigenetic regulators, may affect cancer development and progression and thus, targeting epigenetic regulators provides potential avenues for cancer treatment. Bromodomain and extra terminal domain (BET) proteins, epigenetic readers recognizing histone acetylation, and Sirtuins (SIRT1–7), histone deacetylases or erasers, affect the chromatin acetylation status, and thus have a vital role in transcriptional regulation of a variety of cancer-related genes. Here, the effects of three BET inhibitors on SIRT expression were screened in a broad set of cancer cell lines to study the potential interplay of these distinct epigenetic factors in gene regulation. We show that BET inhibitors have distinct effects on SIRTs and their target gene expression in cancer cell lines derived from several solid tumour cancers. This functional link may open further avenues for epigenetic combination therapies for different cancers.

Keywords

• Sirtuin
• Bromodomain
• Cancer
• Cancer epigenetics
• BET inhibitors