New Study Reveals the Molecular Mechanism of Transcription Factor ‘Surveying’ The Genome of Cells

Transcription factors (TFs) are specific proteins that regulate gene expression, which can search for and bind specific regions in the entire genome to regulate gene expression. We all know that transcription factors not only bind to specific DNA sequences, but also bind non-specifically to any DNA strand. These non-specific associations can significantly increase the ability of transcription factors to find specific targets. However, researchers are not aware of how the efficiency of more than 1,500 transcription factors in the human body changes when scanning large numbers of genomes, localization, and binding to specific sites.


Recently, a research report published in the Nature Communications, scientists from the Federal Institute of Technology in Lausanne, Switzerland, discovered a new method that can help predict the efficiency of scanning transcription of different transcription factors in living cells. In the article, the researchers studied 501 transcription factors in the mouse body and observed how they bind to mitotic chromosomes. This feature associates the ability of transcription factors with DNA in a non-specific manner.



With photobleaching assays and single-molecule imaging techniques, scientists have discovered that it is possible to predict the movement of transcription factors in the nucleus and the efficiency of their binding to specific sites by binding to mitotic chromosomes. Combining the above experiments with the transcription factor maps of the entire silver family, the researchers found that different transcription factors showed three orders of magnitude differences in their ability to find their binding sites. Transcription factors with strong non-specific DNA binding properties are often associated with mitotic chromosomes, which move slowly in the nucleus, but they are effective in finding specific sequences that need to be bound and regulating gene expression.


Researcher David Suter said that transcription factors vary widely in their ability to scan for specific binding sites and that these differences can be predicted by simply observing the number of mitotic chromosomes bound during the period. Transcription factors that can function effectively in the genome often drive a wide range of changes in gene expression patterns, even at lower concentrations, and this is especially important for the decision-making process of cell fate.




Mahé Raccaud, Elias T. Friman, Andrea B. Alber, et al. Mitotic chromosome binding predicts transcription factor properties in interphase. Nature Communications 30 January 2019. DOI: 10.1038/s41467-019-08417-5

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