CRICCHI Emanuele

Cricchi.jpeg Supervisore: Prof. Brancolini
Investigation on epigenetic complexes overseeing articulate decisions on cell fate in human health
In the regulation of human genome, a key function is exerted by epigenetic modifications. They are altered in several human diseases, including cancer. Two elements target of epigenetic modifications are Typical Enhancers (TEs) and SuperEnhancers (SE). Typical epigenetic markers of these regions are H3K27ac and H3K4me1. H3K27ac is under control of two antagonist protein families: Lysine Acetyl-Transferases (KATs) and Histone DeACetylases (HDACs). Cass IIa HDACs, including HDAC4, HDAC5, HDAC7 and HDAC9, plays a key role in the tumorigenesis of leiomyosarcoma (LMS). LMS patients with engaged hypoxia conditions have a lower OS rate with respect to non-altered ones. The main transcription factor supervising cellular response to hypoxia is HIF-1α, which stability and activity during hypoxic conditions may be regulated by HDACs IIa. The aim of my project is to understand the influence of HDACs IIa in hypoxia response in LMS cells. HDAC4-knockout and wt LMS cells will be evaluated for HIF-1α stabilization and hypoxia genes expression using Western Blot assays and qRT-PCRs. End-point ChIP and ChIP-seq analysis using H3K27ac and H3K4me1 will define TEs and SEs. Another epigenetic modification under HDACs IIa regulation, H2BK120ac, will be used as ChIP target to evaluate differences in HDACs activity in normoxia and hypoxia and understand HDACs IIa target regions in hypoxia. Results validation and genetic expression analysis will be performed through RNASeq.