Characterization of the role of H2A.B3 epigenetic regulator in spermatogenesis and male fertility

Our DNA is packaged into a dynamic structure known as chromatin. The basic unit of the chromatin, the nucleosome, is formed by two tightly wrapped superhelical turns of DNA around a histone octamer (H2A-H2B dimer and H3-H4 tetramer). Different epigenetic-based mechanisms regulate the function of chromatin. They include, but not limited to, histone post-translational modifications and the substitution of core histones with their variant forms.

The exchange of histone H2A with its variant forms represents one of the most dramatic and essential alterations to the structure and function of chromatin. Previously, we have discovered a new histone variant in the mouse, H2A.B.3 (formerly known as H2A.Lap1), is uniquely expressed in the testis, brain and upregulated in Hodgkin lymphoma (Soboleva et al. 2011). It has been shown that H2A.B.3. is involved in activating expression and co-transcriptional splicing of genes by being targeted to their transcription start site and exon/intron boundaries (Soboleva et al. 2017). Remarkably, we discovered a completely novel function for histones, direct interaction with RNA, thus implicating chromatin function in RNA processing.

This project aims to decipher the role that epigenetic factors play in heat stress and male fertility. It will utilize a H2A.B3 knockout mouse model that we have recently created to understand the function of H2A.B3 in stress response, and more widely, how the epigenetic mechanisms control the stress response, a number of cutting edge methods will be employed to analyse the epigenetic landscape before and after the heat stress in the presence or absence of H2A.B3.

This project is an all-rounder way to fully immerse into scientific life. It will give you the opportunity to master your experimental skills, learn some of the state-of-the-art techniques, as well as find out a lot about very exciting fields of biology, such as epigenetics and its role in  control of  spermatogenesis and carcinogenesis.