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Proteins help each other stably bind to DNA

It is less known that how DNA helix is neatly packed and stored inside cells. DNA is wound around protein structures known as histones. It forms an elegant, tightly packed structure known as chromatin.

For molecular processes to use that information, the chromatin needs to open and make the DNA available for binding by transcription factors. Transcription factors are proteins involved in the process of converting or transcribing DNA into RNA.

The proteins translate the DNA sequence made of base pairs into messenger RNA. This mRNA is then finally read by a ribosome to produce proteins based on the original blueprint.

Scientists from Tokyo Metropolitan University have uncovered a unique mechanism where two transcription factors stabilize each other’s binding to DNA in fission yeast. They found that Atf1 and Rst2 helped each other stably bind when they were close enough together.

Both proteins transcribe a gene that deals with poor glucose environments but belongs to entirely independent activation pathways.

Scientists studied how transcription factors (TF) bind to the chromatin by looking at a simpler organism, the fission yeast. They wanted changes in their environment.

Now, scientists have successfully caught a glimpse into the unique mechanism behind how transcription works in yeast cells responding to a lack of glucose in their surroundings.

Starved yeast cells cause two TFs, Atf1, and Rst2 to activate transcription of the fbp1 gene. When scientists studied the process, they found that not only that the activation of both was crucial to the function of fbp1, but that they helped stabilize each other.

Scientists also showed that this was due to how close these sites were, usually 45 base pairs apart.

Introduction of extra lengths of DNA between these sites, the TFs suddenly could not help each other. This also closed chromatin, hence leaving both factors unbound. Their relative orientation along the twisting grooves of the helix also proved vital.

Importantly, this effect was shown to be strong enough to counteract the effects of Tup11 and Tup12, co-repressors that help destabilize the random binding of independent TFs to the chromatin. All this suggests that this reciprocal relationship helps the TFs bind successfully and prevents either from attaching by themselves.

A fascinating fact is Completely independent chemical pathways activate TFS.

The process discovered by the team thus integrates these routes into a signal “hub.” Though a single piece in a complex biochemical puzzle, this finding helps highlight an unappreciated mechanism by which different TFs interact and effectively integrate pathways. The team hopes this new insight can help in the fight against cancer and other related illnesses.

Journal Reference:
  1. Wakana Koda, Satoshi Senmatsu et al. Reciprocal stabilization of transcription factor binding integrates two signaling pathways to regulate fission yeast fbp1 transcription. DOI: 10.1093/nar/gkab758

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