Transcription factors are proteins that can bind to DNA and affect the expression of genes; some are known as master regulators that can have a wide impact and affect crucial processes like development. Two new studies have added to what we know about these important sequences and how they function.
Reporting in Nature, researchers have characterized sequences in the human genome that may act as cis-regulatory elements (CREs), which are sequences that can bind to transcription factors and help regulate the activity of nearby genes. The study focused on three cell types, and used computational tools to model genetic activity. The work found that almost half (41.7%) of the candidate CREs were active in these cells.
This research opens the door to future work that can analyze how variations in the sequences of these CREs can contribute to disease. The data is now publicly available.
The genomic sequences that transcription factors bind to are closely connected to how they function. In another, unrelated study, researchers created an atlas of sites in the genome where transcription factors can bind. The findings have been reported in Genome Research.
This work may help us learn more about various diseases and conditions including some types of cancer and developmental disorders, suggested Genome Research study co-author Bridget Lear, PhD, a research associate professor at Northwestern University.
In this work, the scientists used two common molecular research models: the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans to find genomic sequences that are related to the regulation of other genes. The investigators tagged more than 90 percent of the transcription factors in the fruit fly genome that are known, while 60 percent of known C elegans transcription factors were tagged. Then, they found the sequences that those transcription factors interacted with, and created a dataset of those binding sequences.
This work showed that in fruit flies, the known 605 transcription factors can bind to 3.6 million places the fruit fly genome. In C elegans, 356 known transcription factors could bind to 0.9 million genomic locations in the roundworm models.
“This study indicates that most genes are likely regulated by multiple transcription factors and suggests that complex interactions between these factors influence the patterns and levels of gene expression. The establishment of this comprehensive dataset represents an important step towards understanding how genes are regulated,” said Lear.
Sources: Northwestern University, Genome Research, Kyoto University, Nature
