Unravelling the enigma of why humans require seven distinct histone deacetylase complexes - implications for therapeutic intervention

There are seven families of class I histone deacetylase complexes that play a role in many cellular processes, such as cancer, cell cycle progression and DNA repair. Investigating how these HDAC complexes act to control gene expression and their interactions with other proteins should lead to an understanding of their influence in the cell.
HDAC inhibitors are currently used to treat some cancers, epilepsy and schizophrenia. They are also promising therapeutics for a number of other diseases such as spinal muscular atrophy, Friedrich's ataxia, Alzheimer's disease, HIV infection and heart disease. An understanding of the structure and function of the different histone deacetylase complexes will allow inhibitors to be designed against specific complexes to reduce side effects (for a review Millard et al. 2017).
We hope to unravel the contributions of each HDAC complex to gene expression in the cell using a range of techniques such as: Chromatin immunoprecipitation using anti-FLAG antibodies to enable comparison between genome locations of the seven complexes; Protac-mediated destruction of the complexes to identify changes in gene expression and histone acetylation using RNAseq and ChIP; Mass spectrometric analysis of the proteomes associated with each of the complexes using the RIME approach.