Some transcription factors act quickly to reactivate genes in new cells. Image credit: Adapted from Owens, Papadopoulou et al. (CC BY 4.0)
A single cell contains several meters of DNA which must be tightly packaged to fit inside. Typically, the DNA is wound around proteins, like a thread around many spools, to form more compact structures called nucleosomes. Before a cell divides in two, however, it needs first to access and replicate its DNA so that each new cell can get a copy of the genetic material. The cell then needs to condense the DNA again so that the two copies can be easily separated via a process called mitosis. These two processes – DNA replication and mitosis – entail major rearrangements of the nucleosomes, which then need to be returned to their original positions.
Nucleosomes are also repositioned when cells need to access the coded instructions written in genes. Molecules called transcription factors bind to targets within the DNA to make sure genes are active or inactive at the right times of a cell’s life, but many are evicted from the DNA during its replication and during cell division. Most transcription factors also require nucleosomes to be specifically organized to bind to the DNA, and it remains unclear how the factors re-engage with the DNA and how nucleosomes are managed during and after DNA replication and mitosis.
Owens, Papadopoulou et al. set out to understand how nucleosomes are organized immediately after DNA is replicated and while cells divide. Experiments with mouse cells grown in the laboratory showed that certain transcription factors can rebind to their targets within minutes of replication finishing, remain bound to the DNA during cell division, and displace nucleosomes from their binding sites. Owens, Papadopoulou et al. refer to these factors as “resilient transcription factors” and identified two examples, named CTCF and Esrrb. Further experiments showed that, by maintaining the structure of nearby nucleosomes while a cell divides, these resilient transcription factors could quickly reactivate genes immediately after DNA replication and mitosis are complete.
These findings show that transcription factors play a fundamental role in maintaining gene regulation from one generation of cells to the next. Further studies on this topic may eventually foster progress in research areas where cell division is paramount, such as regenerative medicine and cancer biology.
