Gene regulation is the process of controlling gene activity in response to cellular needs. While every cell contains the same DNA, different cells have distinct characteristics due to variations in gene regulation. This complex process involves enhancers and transcription factors (TFs).
Enhancers are short DNA sequences that increase the likelihood of a gene being activated. TFs bind to enhancers and control gene expression by flipping on/off switches. There are over 1600 TFs in the human genome, making it challenging to understand how they interact.
Researchers have traditionally focused on identifying specific DNA motifs recognized by potent TFs. However, this approach has failed to explain the complexity of gene regulation. Instead, scientists have discovered that enhancer context is crucial for understanding how multiple TFs cooperate to regulate gene expression.
A recent study led by Judith Kribelbauer at EPFL has shed light on the interplay between enhancers and TFs. The researchers developed a new approach using chromatin accessibility quantitative trait loci (caQTL) mapping, which revealed “context-only” TFs. These proteins boost the activity of TFs that establish cellular identity.
The study found that context-only TFs do not directly initiate gene activity but are crucial in creating a cooperative environment for efficient regulation of important genes. They also discovered that these TFs do not need to be in direct proximity to the TFs they enhance, suggesting a more flexible and dynamic collaborative mechanism.
Another significant finding was the role of context-only TFs in forming regulatory factor clusters essential for maintaining cell identity. These clusters can form complex networks of enhancers that work together to regulate gene expression, making the process adaptable to different cellular needs.
This study provides a framework for understanding how different TFs cooperate in various cellular contexts, which could lead to more targeted and effective genetic therapies.
Source: https://phys.org/news/2024-09-context-specific-factors-gene.html