GPS2 and HDAC3 RNA-Seq in GPS2-KO MCF-7 [RNA-Seq]

Within the nucleus, G-Protein Pathway Suppressor 2 (GPS2) was first recognized as a component of the core NCoR/SMRT corepressor complex. This is a multi-protein complex that functions as a corepressor for a variety of transcription factors, including nuclear receptors, and promotes the deacetylation of histones on target regulatory regions via its main catalytic unit, the histone deacetylase HDAC3. Based on this association, GPS2 was initially characterized as a transcriptional corepressor, with transcriptomic analysis of various KO/KD models confirming its role in contributing to the repression of inflammatory genes targeted by the NCoR/SMRT complex. To address this knowledge gap, we asked whether GPS2's dual role in transcription could be attributed to the stabilization of distinct chromatin remodeling factors, with the hypothesis that stabilization of other enzymes may, in turn, affect post-transcriptional modification of histone marks in different directions. In particular, we investigated whether GPS2 presence in the NCoR/SMRT complex may prevent HDAC3 ubiquitination. Our results confirmed that lack of GPS2 leads to aberrant HDAC3 ubiquitination and its dismissal for its target genes.