Today’s guest post is by Anna Drangowska-Way, PhD, a freelance science writer based in Poland. Anna is working with non-profit organizations, promoting open research practices, and writing about recent scientific discoveries. Connect with Anna on LinkedIn
All cells in the body have the same DNA code, yet the number of different cell types produced by that DNA code can be enormous. This diversity is the result of tissue-specific gene regulation.
Currently, the researchers believe there are two factors that have a major impact on tissue-specific gene expression. First, chromatin accessibility—whether the DNA in a given section is unwound enough that the protein necessary to copy the DNA into RNA can access it. Second, the presence of regulatory DNA sequences called enhancers, or short DNA sequences that attract specific proteins called transcription factors (TFs) that control gene expression levels.
Integrating experimental data regarding those molecular elements and visualizing how they intersect is challenging, and currently available tools are insufficient and not user-friendly. This inspired the researchers to build VIDEO—Visual Integration of Drosophila Enhancer Organization which is documented in this GENETICS study. VIDEO is a tool that requires no programming knowledge and allows visualization of TF binding motifs within gene enhancers in Drosophila.
Using VIDEO, researchers can generate new insights, as in the example the authors provide where they encountered a genetic puzzle worth pursuing further.
The authors used VIDEO to identify candidate TFs important for hindgut (the rear part of the digestive tract) development. Two of the top differentially expressed TFs identified were orthopedia (otp) and brachyenteron (byn).
They made an interesting observation regarding the relationship between the two TFs and their binding motifs. First, previous research showed that otp expression in the hindgut is activated by byn. Additionally, the otp promoter has byn motifs, which was also confirmed using VIDEO, along with the identification of an otp motif in the otp promoter.
Using VIDEO, the researchers identified otp and a byn motifs in the byn promoter. Such an arrangement of motifs suggests potential autoregulation or cross-regulation, especially given that homologs of this TF family have been shown to autoregulate in different species. Other work, however, suggested a lack of autoregulation of byn in Drosophila. The authors suggest possible explanations, such as sites being conserved across species but non-functional in Drosophila, or functional but only in certain biological contexts. To get an answer, experimental work is still necessary.
Beyond generating interesting hypotheses regarding tissue-specific gene regulation, this paper guides the reader through the VIDEO pipeline. As the authors explain, the user can start with a gene list and identify transcription factors expressed in each tissue, as well as the binding motifs of those TFs located within enhancers of a selected gene set.
Users can also enter gene lists and already selected motif data so the program can scan the gene list for motif occurrences. If available, the user can also add chromatin accessibility and/or in vivo TF-binding data to their gene lists. This will allow the program to filter the motif occurrences to open chromatin or TF-binding regions and create an interactive plot of the results.
VIDEO combines many functions into a single user-friendly tool, allowing Drosophila researchers to gain novel insights into new and existing data sets and tissue-specific gene regulation.
References
Ajay V, Laughner N, Cahan P, Andrew DJ, VIDEO—Visual Integration of Drosophila Enhancer Organization: a tool for integrating and visualizing chromatin accessibility, in vivo transcription factor binding and motif occurrence in tissue-specific differentially expressed genes, GENETICS, 2026, iyag117. https://doi.org/10.1093/genetics/iyag117