SUPR
Quantitative Epigenomics of Early Development
Dnr:

NAISS 2024/22-108

Type:

NAISS Small Compute

Principal Investigator:

Simon Elsässer

Affiliation:

Karolinska Institutet

Start Date:

2024-02-01

End Date:

2025-02-01

Primary Classification:

10610: Bioinformatics and Systems Biology (methods development to be 10203)

Allocation

Abstract

We are inteterested in the dynamic regulation of chromatin in stem cells and differentiation (e.g. Kumar et. al., Cell Reports, 2019; Navarro et. al., Nat Comms, 2020; Kumar et. al., Nat Cell Bio, 2022, Weigert etl. al. Nat Cell Bio, 2023). ChIP-Seq allows to determine the occupancy of a cellular factor of interest on a given sequence of DNA. While often perceived and interpreted as quantitative method, traditional ChIP-Seq can only provide a qualitative measure because of the lack of internal or external reference for normalization. In 2022, we will further develop various genome-wide profiling methods, including single cell methods, and expand a number of collaborations studying the role of epigenetic modifications and nuclear organization on the regulation of pluripotency, lineage commitment and cancer. We also started to intensify proteomics projects, which we also process on Uppmax using MaxQuant. Recent publications Kumar B*, Navarro C*, Winblad N*, Schell JP, Zhao C, Weltner J, Baqué-Vidal L, Mantero AS, Petropoulos S, Lanner F, Elsässer SJ, “Polycomb Repressive Complex 2 shields naïve human pluripotent cells from trophectoderm and mesoderm differentiation”, Nature Cell Biology (2022) Larsen BD, Benada J, Yung PYK, Bell R, Pappas G, Urban V, Ahlskog JK, Kuo TT, Janscak P, Megeney LA, Elsässer SJ, Bartek J, Sørensen CS, “Cancer cells utilize self-inflicted DNA breaks to evade growth limits imposed by exogenous genotoxic stress”, Science (2022) Weigert R*, Hetzel S*, Bailly N*, Haggerty C, Yung PYK, Ilik IA, Navarro C, Bolondi A, Kumar AS, Anania C, Brändl B, Meierhofer D, Lupianez DG, Mueller FJ, Aktas T, Elsässer SJ, Kretzmer H, Smith ZD, Meissner A, “Dynamic antagonism between key repressive pathways in the placental epigenome“, Nature Cell Biology (2023) Schlesinger D, Dirks C, Navarro C, Lafranchi L, Eirich J, Elsässer SJ. A large-scale sORF screen identifies putative microproteins and provides insights into their interaction partners, localisation and function. bioRxiv. (2023) - in revisions