Differential Notch target genes expression profile upon HDAC3 loss-of-function.

The Notch signaling pathway regulates several differentiation and developmental processes in both pre- and post-natal life and its aberrant regulation leads to diseases, including cancer. Here, we investigated the role of histone deacetylase 3 (HDAC3) on the regulation of the Notch-dependent gene expression program in mouse pre-T (Beko) cells. We first defined Notch target genes as those genes that are downregulated upon inhibition of the Notch pathway using DAPT, a gamma-secretase inhibitor (GSI). Subsequently, we investigated the role of HDAC3 in the regulation of Notch target genes by shRNA- and pharmacologically (apicidin)-mediated loss-of-function of HDAC3. Overall design: Mouse pre-T cells (Beko) were treated with gamma-secretase inhibitor (GSI) DAPT to identify Notch target genes by RNA-seq analysis. The function of HDAC3 at Notch target genes was investigated by shRNA- or pharmacological (Apicidin)-mediated loss-of-function of HDAC3 followed by RNA-seq analysis.