Project (Marieke Oudelaar)

Precise regulation of gene expression during development is a cornerstone for complex biological life. Mammalian gene expression patterns are controlled by the cis-regulatory elements of the genome, which include enhancers promoters. The spatial organization of the genome in the nucleus is important for communication between these elements. Enhancers and promoters interact in three-dimensional chromatin structures, which allow for specific communication between elements that are separated by large genomic distances. These enhancer-promoter interactions are important for gene regulation and perturbations of such interactions underly several congenital disorders and cancers.

In our lab, we study the interplay between the structural organization of the genome in the nucleus and the regulation of gene expression, and how perturbations in these processes contribute to disease. We develop and use state-of-the-art functional genomic techniques, in combination with genetic perturbations and computational approaches. We offer exciting research projects, usually involving a combination of experimental and computational work, in a stimulating and supportive research environment. We are looking for highly motivated students with a background in molecular biology, biochemistry, genetics or bioinformatics and a strong interest in gene regulation and genome organization.

• Mauksch C, Zhu Y, Velychko T, Sagropoulou S, Aljahani A, Ramasamy S, Žumer K, Oudelaar AM* (2025) FACT depletion demonstrates a role for nucleosome organization in TAD formation. Molecular Systems Biology https://www.embopress.org/doi/full/10.1038/s44320-025-00165-7
  
  
• Karpinska MA, Zhu Y, Fakhraei Ghazvini Z, Ramasamy S, Barbieri M, Cao NTB, Varahram N, Aljahani A, Lidschreiber M, Papantonis A, Oudelaar AM* (2025) CTCF depletion decouples enhancer-mediated gene activation from chromatin hub formation during cellular differentiation. Nature Structural & Molecular Biology 32, 1268-1281 DOI:10.1038/s41594-025-01555
  
  
• Papantonis A* and Oudelaar AM* (2025) Mechanisms of enhancer-mediated gene activation in the context of the 3D genome. Annual Review of Genomics and Human Genetics 26:4.1–4.26 DOI: https://doi.org/10.1146/annurev-genom-120423-012301
  
  
• Žumer K*, Ochmann M, Aljahani A, Zheenbekova A, Devadas A, Maier KC, Rus P, Neef U, Oudelaar AM*, Cramer P* (2024) FACT maintains chromatin architecture and thereby stimulates Pol II pausing during transcription in vivo. Molecular Cell 84, 1-17 DOI:10.1016/j.molcel.2024.05.003
  
  
• Oberbeckmann E*, Quililan K, Cramer P, Oudelaar AM* (2024) In vitro reconstitution of chromatin domains shows a role for nucleosome positioning in 3D genome organization. Nature Genetics 56, 483-492 DOI:10.1038/s41588-023-01649-8
  
  
• Ramasamy S, Aljahani A, Karpinska MA, Cao NTB, Cruz JN, Oudelaar AM* (2023) The Mediator complex regulates enhancer-promoter interactions. Nature Structural and Molecular Biology 30, 991-1000 DOI:10.1038/s41594-023-01027-2
  
  
• Aljahani A, Hua P, Karpinska MA, Quililan K, Davies JOJ, Oudelaar AM (2022) Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF. Nature Communications 13, 2139 https://doi.org/10.1038/s41467-022-29696-5
  
  
• Oudelaar AM* and Higgs DR* (2021) The relationship between genome structure and function. Nature Reviews Genetics 22, 154-168 DOI: https://www.nature.com/articles/s41576-020-00303-x