Genome Organization and Gene Regulation
The group will transfer from University of Copenhagen to Danish Cancer Institute by March 1, 2025
Our research
In the Genome organization and gene regulation group, we aim to understand how the folding of genomes contributes the regulation of gene expression programs in health and disease, such as cancer.
The Krietenstein groups studies how genomes are folded in 3D space. Human genomes are consisting of 3 billion base pairs of DNA. In each cell 2 meters of DNA are stored in the nucleus, a spheric compartment with a 10 micrometer in diameter. Only 1-2% of this DNA encodes for proteins, the machines that catalyze biochemical reactions in cells. However, mutations that lead to cancer are often located elsewhere in the genome and are though to regulate the expression levels of genes rather than changing their nature. How and when these mutations develop a deleterious role that leads to malignant gene expression programs remains elusive.
The Krietenstein lab studies the role of genome folding in gene regulation in health and disease. Distal regulatory elements, called enhancers, that are distributed thought the non-coding genome modulate the expression of distal genes. This mechanism of gene regulation is important organismal development as it allows cells to develop many different cell types from one and the same genome. However, mutations within the genome and erosion of the epigenome can deregulate these programs and lead to cancer. We aim to understand how distal elements in the genome can regulate and change the expression levels of genes mechanistically. We leverage innovative 3D-genomics approaches that allow us to measure the structure of genomes with ultra-high resolution to understand the mechanisms behind how mutations in the non-coding genome lead to cancer.
Metelova M, Krietenstein N: Deciphering histone mark-specific fine-scale chromatin organization at high resolution with Micro-C-ChIP. bioRxiv preprint 2023
Krietenstein N, Abraham S, Venev SV, Abdennur N, Gibcus J, Hsieh T-HS, Parsi KM, Yang L, Maehr R, Mirny LA, Dekker J, Rando OJ: Ultrastructural Details of Mammalian Chromosome Architecture. Mol Cell 2020; 78(3):554-565
Oksuz BA, Yang L, Abraham S, Venev SV, Krietenstein N, Parsi KM, Ozadam H, Oomen ME, Nand A, Mao H, Genga RMJ, Maehr R, Rando OJ, Mirny LA, Gibcus JH, Dekker J: Systematic evaluation of chromosome conformation capture assays. Nat Methods 2021; 18:1046-1055
Krietenstein N, Rando OJ: Mesoscale organization of the chromatin fiber. Curr Opin Gen Develop 2020: 61:32-36
Krietenstein N, Wal M, Watanabe S, Park B, Peterson CL, Pugh BF, Korber P: Genomic Nucleosome Organization Reconstituted with Pure Proteins. Cell 167(3):709-721
Group leader: Nils Krietenstein
During his doctoral work in Munich (Germany), Nils studied the basic packing mechanisms that organize our genomes as chromatin in 1-dimensinal space. As a postdoctoral researcher (Worcester, USA), Nils developed protocols that allow researchers to measure the 3-dimensional folding of entire genomes. He started his group in October 2021 in Copenhagen. Nils was awarded the Lundbeck Foundation Fellowship Award to expand and establish 3D genomics in the danish research landscape. The Krietenstein Lab will be part of the DNRF Center of Excellence EpiC led by Anja Groth.
ORCID: 0000-0003-2519-6305
Staff
Contact information for all staff in GOG will appear later
Key funding