image: MAbID in a nutshell. Left: antibodies, each binding a specific histone modification or protein, are merged with individual cells. After these antibodies have bound, a small barcode is attached to the adjacent DNA using the MAbID procedure. Right: these barcodes are then read, allowing the location of each histone modification on the DNA to be determined for each individual cell. This information allows the creation of cellular atlases that clearly identify the similarities and differences between cells.
Credit: Credit: Robin van der Weide. Copyright: Hubrecht Institute.
Researchers from the group of Jop Kind developed a new technique called MAbID. This allows them to simultaneously study different mechanisms of gene regulation, which plays a major role in development and disease. MAbID offers new insights into how these mechanisms work together or against each other. The results were published in Nature Methods on the 4th of December.
DNA is the most important carrier of genetic information. Each cell contains approximately two meters of DNA. To ensure that all this genetic material fits into the small cell nucleus, it must be tightly packed. The DNA is therefore wrapped around a special type of protein, a histone. The packages of DNA and histones are called chromatin.
Reading DNA
Chromatin not only ensures that all the DNA fits into the cell, it also determines which parts of the genetic material can be read by the cell. For example, a piece of DNA that is tightly wrapped around the histone is more difficult to read than a piece of DNA that is packed more loosely. Ultimately, the way in which chromatin is folded determines which parts of the genetic material are expressed and which parts are not. This pattern of gene expression differs per cell type. Different genes are active in a skin cell than in a liver cell, for example.
Changes in chromatin
The activity of genes is not always the same: a different pattern of genes may be active in one moment compared to another. That is because the structure of chromatin can change. For instance, changes can occur in the histones, which are called histone modifications. Certain proteins can also bind to the chromatin. Both processes influence the readability of the DNA and therefore the gene expression.
New technique
In recent years, various technologies have been developed to investigate the mechanisms of gene regulation. However, there was still a technique missing to allow researchers to simultaneously look at multiple mechanisms in one cell. The group of Jop Kind therefore designed a new technique: MAbID. With MAbID, researchers can simultaneously study multiple types of histone modifications and the proteins that bind to chromatin.
Working together
“With our new technique, we can see how the different mechanisms of gene expression are connected, for example how they work together or against each other. And the great thing is that we no longer need separate experiments for this, we can study everything at once in each individual cell. That makes the research much more efficient,” Silke Lochs, one of the researchers on the project, explains.
Applications
The technology can be widely applied. Robin van der Weide, another researcher on the project, says: “MAbID can help us answer fundamental scientific questions, for example about how gene regulation works during the development of humans or animals. But we can also use it for research into the development of diseases that can be caused by abnormalities in gene regulation, such as cancer.” The versatile new technology can therefore in the future provide important insights into both health and disease.
Publication
Combinatorial single-cell profiling of major chromatin types with MAbID. Silke J.A. Lochs*, Robin H. van der Weide*, Kim L. de Luca, Tessy Korthout, Ramada E. van Beek, Hiroshi Kimura and Jop Kind. Nature Methods, 2023.
* Authors contributed equally.
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About Jop Kind
Jop Kind is group leader at the Hubrecht Institute, professor by special appointment of Single Cell Epigenomics at the Radboud University Nijmegen and Oncode Investigator. His group is interested in elucidating the role of chromatin and nuclear architecture in gene-regulation and DNA-repair. The Kind group develops new techniques, such as the recently developed DamID and m6ATracer techniques. These techniques enable them to study genome architecture and protein-DNA interactions in high resolution in single cells. The Kind group uses these techniques to study the role of genome architecture and chromatin context in temporal and spatial control of gene expression in development and disease.
About the Hubrecht Institute
The Hubrecht Institute is a research institute focused on developmental and stem cell biology. Because of the dynamic character of the research, the institute has a variable number of research groups, around 20, that do fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit www.hubrecht.eu.
Journal
Nature Methods
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Combinatorial single-cell profiling of major chromatin types with MAbID
Article Publication Date
4-Dec-2023
COI Statement
The authors declare the existence of a competing interest, J.K. and S.J.A.L. are inventors on a patent application (PCT/NL2022/050635, applicant: Koninklijke Nederlandse Akademie Van Wetenschappen) related to the MAbID technology. The remaining authors declare no competing interests.