Bioengineering experts at Ecole Polytechnique Fédérale de Lausanne have discovered how to predict effectiveness with which transcription factors (TFs) find places that need to be bound to regulate gene expression.
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This finding could help researchers determine which TFs are most effective in managing changes in gene expression patterns and influencing the fate of cells.
Genetic transcription is the first step that is required for protein production, and TF is the protein that regulates this process. They work by scanning DNA and binding to specific sequences that "turn" the "on" or "off" genes.
As well as binding to specific DNA regions, it is also known that transcription factors are not specifically related to any random DNA sequences. This nonspecific binding can optimize the efficiency at which TF is located at its specific binding sites by allowing them to move along the DNA.
However, scientists have yet to understand why many hundreds of TFs in humans differ in their ability to locate those specific binding sites.
Now David Suter and colleagues found that the answer lies in their ability to bind to "mitotic" chromosomes.
Using photobleaching and imaging a single molecule to study 501 TF in the mouse model, the team found that the binding of the mitotic chromosome can predict the TF motion in the nucleus and the efficacy with which they localize the binding sites.
Other studies combining these experiments with TF mapping of the entire genome showed which TF had the strongest non-specific DNA binding capability.
Those TFs associated with mitotic chromosomes slowly moved into the nucleus and were particularly effective in localizing the sites they needed to bind to regulate gene expression.
Transcription factors usually differ in their ability to scan the genome to find their specific binding sites, and these differences can be predicted simply by looking at how much they relate to mitotic chromosomes. "
David Suter, senior scientist
"The transcription factors that are most effective in genome search could lead to widespread changes in gene expression patterns, even if they are expressed at low concentrations, and therefore may be particularly important for the decision-making process of cell fate."
How transcription factors examine the genome
Binding of the mitotic chromosome predicts transcription factor properties in the interphase. Natural communications. Jan 2019.
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