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CoREST complexes in gene regulation and development 

Grafik: Igor Macinkovic

 Igor Mačinković

Since its initial discovery in 1999, several hundreds of studies involving CoREST were published. The general belief is that CoREST is associated with histone methylases and deacetylases and that it plays roles in transcriptional regulation and development. However, there are still many open questions about the composition, diversity and functionality of CoREST complexes. A lot is known about mammalian CoREST complexes, but less so about the composition, diversity and functionality for such epigenetic regulators in Drosophila.

The primary goal of this project is to address these questions by the systematic identification and isolation of putative dCoREST-containing complexes in the fly model system. We utilise gel filtration chromatography, affinity purifications, and proteomic interactome analysis to define different CoREST assemblies of the two major dCoREST isoforms: dCoREST-L and dCoREST-M. We have biochemical characterised three distinct Drosophila dCoREST-containing complex (Mačinković et al., 2019). Moreover, we ascribe specific functions to distinct dCoREST complexes by integrating functional genomics methods, such as chromatin immunoprecipitation (ChIP) analysis and combined RNA interference (RNAi) and transcriptome analysis, with proteomics findings.