Johannes Wichmann, Epigenetics & Development division

Johannes Wichmann, Epigenetics & Development division

Start Time: 
Wed, 28/10/2020 - 13:00:00
End Time: 
Wed, 28/10/2020 - 14:00:00

Wednesday seminar hosted by Tim Thomas & Anna Voss

Johannes Wichmann
PhD Student - Thomas/Voss Laboratory, Epigenetics & Development division - Healthy Development & Ageing Theme (this is a PhD completion seminar)


Investigation into the MYST lysine acetyltransferase TIP60 in inducible human and mouse knockout models

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Including Q&A session


Histone acetylation affects the way DNA and associated proteins are packaged in the cell nucleus and regulate chromatin structure and gene expression. Acetylation of core histones has been broadly correlated with initiating and maintaining open chromatin, poised or active gene transcription, DNA damage repair, as well as chromosome condensation and decondensation during mitosis and meiosis. The acetylation of lysine residues is catalysed by histone lysine acetyltransferases (KATs) and deacetylases (HDACs), which are tightly regulated. Dysregulation of KATs and aberrant lysine acetylation has been associated with tumorigenesis and negative prognoses in a wide range of cancer, presenting a new area of potential therapeutic targets.

Characterisation of key mechanisms causing chromosomal aberrations and identifying approaches that can be used to reduce likelihood of genome instability due histone acetylation defects will pave the way for better detection of early changes in cancer and development of therapeutic applications in the future. This work represents important steps towards the development of histone lysine acetyltransferases as drug targets.

During his PhD, Johannes has investigated the effects of acute deletion of the MYST lysine acetyltransferase TIP60 (KAT5) using inducible cre-recombinase and CRISPR/Cas9-mediated deletion in human cells and mouse cells, as well as mouse embryos and its potential role in tumorigenesis. A comprehensive analysis of histone acetylation activity of TIP60 shines light on potential functions in its many proposed roles.