This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Every cell in the body contains essentially the same DNA, yet a brain cell behaves differently from a muscle cell or an immune cell. The difference lies largely in how each cell reads its genetic instructions.
Proteins called transcription factors bind specific DNA sequences and help control when and where genes are active. They direct processes ranging from embryonic development to immune function. When this regulation goes wrong, disease can result.
But although the human genome contains around 1,600 transcription factors, the DNA-binding preferences of many have remained unknown. An international collaboration led by Timothy Hughes at the University of Toronto has now filled many of these gaps in a study published in Nature. The researchers combined five experimental platforms with computational analyses, performing more than 4,800 experiments and identifying DNA-binding motifs for 177 transcription factors that were previously poorly characterized.
The work added around 130 distinct motifs to the known vocabulary of human gene regulation. The work has generated a "Codebook": the most comprehensive catalog of human transcription factor binding preferences assembled to date. Bart Deplancke's lab at EPFL played a central role in developing the Codebook.
"Our genomes contain the instructions for life, but understanding how cells actually read those instructions has remained one of biology's major challenges," says the professor, who is a co-corresponding author of the Nature study. "This work brings us much closer to a complete dictionary of the proteins that control gene expression." But reading DNA is only part of the story. DNA also carries chemical modifications that influence how genes are regulated without changing the sequence itself.
One of the best-known is DNA methylation. In a companion paper published in Nature Communications, Deplancke's team developed meSMiLE-seq, a microfluidic method that compares transcription factor binding to methylated and unmethylated DNA in the same experiment. The researchers used the method to study 114 transcription factors and obtained DNA-binding models for 48.
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