Protein dominoes

Study reveals that transcription, a basic process in gene expression, is happening in sequentially assembled specialized areas in the cell nucleus.

Nanog (green) clusters first to regulate formation of the transcription bodies (magenta, labelled initiation RNA polymerase II) in a living zebrafish embryo. Copyright: Kuznetsova et al., Current Biology (2022)

Our hereditary material, the DNA, is tightly packed to fit into the nucleus of a cell. In a process known as transcription, pieces of DNA are copied into a messenger molecule ¬– the ribonucleic acid (RNA) – that carries the information needed to produce proteins, the building blocks of life. In most organisms, such as mice or zebrafish, transcription happens in certain areas of the nucleus, also called transcription bodies. The activators of transcription are proteins called transcription factors: they bind to specific sites on the DNA and activate the transcription process. How those transcription factors come together to form transcription bodies in a living organism was unclear.

An international research team from the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Center for Systems Biology (CSBD), both located in Dresden, Germany, the University of Lausanne in Switzerland, the Tokyo Institute of Technology in Japan, and the Human Technopole in Milan, Italy investigated several transcription machinery components and how they come together to activate the transcription process. The researchers looked at the early development of a zebrafish embryo, because this is a fitting model to study transcription bodies. They knew already that the transcription factor Nanog is involved in the transcription process of the zebrafish. “We observed several proteins and found that Nanog was the first one that clusters, then others follow, to form transcription bodies,” explains Ksenia Kuznetsova, the first author from the research group of Nadine Vastenhouw, former research group leader at the MPI-CBG and now located at the University of Lausanne. “When we removed Nanog, we could see that the other proteins were not recruited and the transcription bodies did not form.”

This study shows for the first time a sequential recruitment of proteins that form transcription bodies, which are needed for the transcription process, and that transcription factors can organize transcription bodies. Since transcription is a fundamental process in biology, this study provides an important step towards understanding how factors that activate this process are organized so that the appropriate products are made, cells take up the right fate and collectively become the right tissue, and the organism can develop normally.

Original Publication

Ksenia Kuznetsova, Noémie Chabot, Martino Ugolini, Edlyn Wu, Manan Lalit, Haruka Oda, Yuko Sato, Hiroshi Kimura, Florian Jug, Nadine Vastenhouw: "Nanog organizes transcription bodies.", Current Biology, 06. December, 2022, doi: 10.1016/j.cub.2022.11.015