Researchers at Karolinska Institutet present a new method for analyzing how instructions in the genome control how our genes are activated in individual cells.
The results give new insights into how the genome encodes for its own use, which increases our basic understanding of how genes are activated in different types of cell in the body in both good and ill health.
A method to sequence RNA in individual cells
In the study, the researchers used a method which they had developed themselves to sequence RNA in individual cells. The method makes it possible to measure the number of RNA molecules for almost all the genes used in a cell. The researchers sequenced cells of connective tissue and embryonal stem cells from a crossbreed of two distantly related mice. With the help of the natural variation found in the genes of the two different types of mouse, the researchers were able to distinguish between the sequenced RNA from the mother’s and the father’s versions of the gene and in that way measure the transcription exactly. They then used a mathematical model to make estimations, for each of the versions, of how often the gene is transcribed and how much RNA is then produced.
“We have begun to chart how the genome encodes for its own use”
”We discovered that enhancers did affect how often a gene was transcribed in the two different cell types but not how many RNA molecules were produced. We also found that certain DNA sequences located at the beginning of a gene can influence how much RNA is produced in a burst. In that way, we have begun to chart how the genome encodes for its own use,” says Anton Larsson, the first author of the study in question and a doctoral student in Rickard Sandberg’s research group.
”It will be possible to make wide use of our method to chart at a much deeper level how different proteins affect the transcription process,” says Rickard Sandberg, professor at the Department of Cell and Molecular Biology at Karolinska Institutet, who has led the study in question.
The research was funded with support from the European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation and the Vallee Foundation and the results have been published in Nature.
Photo of Rickard Sandberg and Anton Larsson, Department of Cell and Molecular Biology at Karolinska Institutet. Photographer: Stefan Zimmerman