Credit: Buys de Barbanson, copyright Hubrecht Institute 2 January 2023 New methods for research into chromatin Back to news Researchers from the lab of Alexander van Oudenaarden developed new methods to study chromatin in individual cells. Chromatin packs the long strands of DNA into dense structures in order to fit them inside the cell’s small nucleus. Both new methods – one computational and one experimental – allow researchers everywhere to look at any aspect of chromatin within any biological context. Hopefully, these new possibilities facilitate a fast increase in our understanding of chromatin regulation in healthy and troubled organism development. The methods were recently published in Nature Biotechnology and Nature Genetics. Every cell in an organism’s body contains about two meters of DNA. To fit these long DNA strands in the tiny nucleus of the cell, the DNA must be tightly packed. The DNA is therefore wrapped around proteins called histones Proteins in the nucleus around which the DNA is wound. This way, all the DNA fits inside the nucleus. Through modifications of the histones, the DNA is wound tighter or looser, which changes the accessibility of the genes in that area.. The assembly of DNA and histones is called chromatin. Besides densely packing DNA, chromatin determines which parts of the DNA can be read out by the cell. It thereby also influences what genes are active and which ones are repressed. This pattern of gene expression The activity of a gene or genes. The combination of active genes in a cell determines, amongst other things, the function, shape and size of the cell. differs between cell types. Modifications can occur along the tails of the histones, which influences the structure of the chromatin and gene expression. Changes in histones It is known from previous experiments that histone modifications differ between cell types – for example, a skin cell shows different histone modifications than a liver cell. However, with previous methods, researchers needed thousands of cells of the same type to be able to study histone modifications. This limits the types of cells they can look at, because it is simply not possible to obtain that many cells for every cell type. The group of Alexander van Oudenaarden now overcomes this problem by developing two new methods. The first one is experimental and called sortChIC. It allows researchers to look at very rare cell types, such as tissue stem cells. The other method is computational and called scChIX. Researchers can use it to study two histone modifications simultaneously in individual cells. Development With the new methods, researchers everywhere can study any chromatin factor in any biological context in single cells. This is valuable because there are various developmental diseases in humans, including pediatric cancer, that are attributed to mistakes in histone modifications. However, because of the previous methodical limitations, it is not yet clear what exactly goes wrong on the level of the chromatin. The new methods hopefully facilitate a fast increase in our understanding of chromatin regulation during healthy and troubled organism development. Facility With support from Oncode, the facility Single cell core has been created within the Hubrecht Institute to make these and other methods accessible to a broader scientific community. Publications scChIX infers dynamic relationships between histone modifications in single cells. Jake Yeung, Maria Florescu, Peter Zeller, Buys Anton de Barbanson, Max D. Wellenstein & Alexander van Oudenaarden. Nature Biotechnology, 2023. Single-cell sortChiC identifies hierarchical chromatin dynamics during hematopoiesis. Peter Zeller, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson, Vivek Bhardwaj, Maria Florescu, Reinier van der Linden & Alexander van Oudenaarden. Nature Genetics, 2022. Alexander van Oudenaarden is group leader at the Hubrecht Institute and professor of quantitative biology of gene regulation at the University Medical Center Utrecht and Utrecht University. The image at the top of this page was made by Buys de Barbanson, one of the authors on both papers discussed.