Ecole Polytechnique Fédérale de Lausanne bioengineers have discovered how to predict the effectiveness with which transcription factors (TF) find the sites they need to be able to bind to regulate gene expression.
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Discovery can help researchers identify which TFs are most effective in driving changes in gene expression patterns and cell fate.
Gene transcription is the first step required for protein production and TF is the protein that regulates this process. They work by scanning DNA and linking to special sequences that turn the genes on or off.
It is known that not only binding to specific DNA regions, but also transcription factors bind to non-specific binding to any random DNA sequence. This non-specific relationship can optimize the effectiveness of TF at home in its specific binding site, allowing them to slide through DNA.
However, scientists do not yet understand why many hundreds of TF people differ from their ability to find these specific binding sites.
Now David Suter and colleagues have found that the answer is related to their ability to bind to "mitotic" chromosomes.
Using photobleaching and single-molecular imaging to study the 501 TF mouse model, the team found that mitotic chromosomal binding could predict TF motion in the nucleus and the effectiveness with which they bind binding site.
Further studies, in which these experiments were combined with TF mapping of a whole genome, showed which TFs were the strongest non-DNA binding abilities.
Those TFs associated with mitotic chromosomes moved slowly into the nucleus and were particularly effective in finding the sites they needed to associate with gene expression.
Transcription factors differ greatly in their ability to scan the genome to find their specific binding sites, and these differences can be predicted by simply looking at how much they bind to mitotic chromosomes.
David Suter, Senior Researcher
"Transcription factors that are most effective in searching for a genome could lead to profound changes in gene expression patterns, even if they are at low concentrations, and can therefore be particularly important for processes that affect cell fate."
How transcription factors reveal the genome
The mitotic chromosomal binding involves the properties of transcription factors in the intermediate phase. Natural communication. January 2019
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