Gabriela Hayward-Lara, Matthew D Fischer, and Mustafa Mir. Dynamic microenvironments shape nuclear organization and gene expression. Current Opinion in Genetics & Development. Volume 86, 2024. 102177. ISSN 0959-437X. https://doi.org/10.1016/j.gde.2024.102177.
Highlights
- Microenvironments are local high concentrations of multiple nuclear factors.
- Microenvironments form due to protein–protein and protein–chromatin interactions.
- Local concentrations of protein modulate binding frequency rather than duration.
- Microenvironments can bridge multiple genes and regulatory elements.
- Microenvironment lifetimes vary and correlate with regulatory function.
Live imaging has revealed that the regulation of gene expression is largely driven by transient interactions. For example, many regulatory proteins bind chromatin for just seconds, and loop-like genomic contacts are rare and last only minutes. These discoveries have been difficult to reconcile with our canonical models that are predicated on stable and hierarchical interactions. Proteomic microenvironments that concentrate nuclear factors may explain how brief interactions can still mediate gene regulation by creating conditions where reactions occur more frequently. Here, we summarize new imaging technologies and recent discoveries implicating microenvironments as a potential driver of nuclear function. Finally, we propose that key properties of proteomic microenvironments, such as their size, enrichment, and lifetimes, are directly linked to regulatory function.