8 July 2021

Cathrin Gräwe and Michiel Vermeulen, theme Cancer development and immune defense, together with the Schübeler and Thomä labs at the FMI in Basel, Switzerland, identified a long-sought-after transcription factor that regulates essential genes in the mouse and human genome. The study is published in Nature.

Proteins known as transcription factors control the expression of genes by binding to specific DNA sequences, referred to as motifs. Many motifs and their associated transcription factors have been extensively studied. However, for some motifs that control essential genes, the associated transcription factors are unknown. One of these motifs, the CGCG element, was characterized by the Schübeler lab using single-molecule footprinting. DNA affinity purifications followed by mass spectrometry led to the identification of the Btg3-associated nuclear protein (BANP) as the transcription factor that interacts with this motif with a very high affinity.

Further characterization of this protein, which was previously thought to repress genes at the periphery of the nucleus, showed that it is a potent activator of essential genes. Upon binding to its motif in the genome, BANP opens up chromatin and activates transcription. Due to its essential role in regulating expression of essential genes, cells die upon depletion of BANP. This might be the reason that BANP and its important function as a transcription factor has previously been overlooked. Future studies investigating BANP and other essential transcription factors will provide more insights in how genes are regulated, which will eventually lead to a better understanding of cellular homeostasis as well as perturbations thereof that result in disease.

Michiel Vermeulen works at the Faculty of Science of Radboud University and is part of the interfaculty research institute RIMLS.

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