Ansgar Zoch Research Group

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Research in a Nutshell 

Defending the integrity of the genome is essential for the continuity of life. We study the defence mechanisms that protect the germline genome, focusing on piRNA-directed repression of transposons. Transposons, mobile genetic elements encoded in our own genome, threaten their host genome through highly mutagenic transposition, copy-pasting their own genetic information into new loci. They harbour strong regulatory elements, which deregulate their local chromatin environment. Transposon genes therefore need to be epigenetically repressed throughout most of life.

The germline, the cell lineage that will eventually make sperm and egg cells, passes on our genetic information to the next generation. Maintaining integrity of the germline genome is thus paramount to ensure fertility and healthy offspring. However, in mammals, foetal germ cells undergo a massive reprogramming event that erases most epigenetic information and reactivates transposon genes.

The piRNA pathway then targets active transposon genes for epigenetic silencing. It identifies active genomic transposon loci through detection of the nascent transcript by PIWI-bound small non-coding RNAs. Failure to silence transposons leads to male infertility in mice and humans. Yet, the mechanisms of how target-recognition induces gene silencing remains enigmatic. We study this unique RNA-directed gene regulation mechanism using an inter-disciplinary approach; bridging the scales from analysis of molecular interactions to in vivo analysis of mouse models.

Our goal is that by deciphering transposon defence mechanisms and their impact on chromatin regulation we will gain fundamental insights into molecular mechanisms of gene regulation and transposon-driven pathologies.

Contact

ansgar.zoch@ed.ac.uk

Publications

1. ^1,2Zoch A, ¹Konieczny G, ¹Auchynnikava T, Rotte N, Stallmeyer B, Heep M, Berrens RV, Schito M, Kabayama Y, Schöpp T, Kliesch S, McLachlan RI, Houston B, Nagirnaja L, O’Bryan MK, Aston KI, Conrad DF, Cook AG, Rappsilber J, Allshire RC, Tüttelmann F, ²O'Carroll D: C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline. ¹joined first author, ²joined corresponding author; Molecular Cell 2024 Feb 7;S1097-2765(24)00050-9. doi: 10.1016/j.molcel.2024.01.014.
2. ¹Vrettos N, ¹Oppelt J, ¹Zoch A, Sgourdou P, Yoshida H, Song B, Fink R,²O’Carroll D, ²Mourelatos Z, et al.: N-terminal arginine methylation enables diversification of PIWI protein function. ¹joined first author, ²joined corresponding author; bioRxiv [Preprint] 2024 Jan 1:2023.12.31.573779. doi: 10.1101/2023.12.31.573779.
3. Schöpp T, Zoch A, Berrens RV, Auchynnikava T, Kabayama Y, Vasiliauskaitė L, Rappsilber J, Allshire RC, O'Carroll D: TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing. Nat Commun. 2020 Jul 27;11(1):3739. 10.1038/s41467-020-17372-5.
4. Zoch A, Auchynnikava T, Berrens RV, Kabayama Y, Schöpp T, Heep M, Vasiliauskaitė L, Pérez-Rico YA, Cook AG, Shkumatava A, Rappsilber J, Allshire RC, O'Carroll D: SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation. Nature. 2020 Aug;584(7822):635-639. 10.1038/s41586-020-2557-5. Epub 2020 Jul 16.
5. Ozata DM, Gainetdinov I, Zoch A, O'Carroll D, Zamore PD: PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 2019 Feb;20(2):89-108. doi: 10.1038/s41576-018-0073-3.

Full publication list can be found on Research Explorer: Ansgar Zoch — University of Edinburgh Research Explorer