Author response: Set1/COMPASS and Mediator are repurposed to promote epigenetic transcriptional memory
Year: 2016
Type: peer-review
Abstract: Cells respond to stressful conditions by changing which of their genes are switched on. Such stress-specific genes are typically switched off again when the conditions improve, but can remain primed and ready to be switched on again when needed. This phenomenon is known as “epigenetic transcriptional memory” and allows for a faster or stronger response to the same stress in the future. In fact, these memories can last for a long time, even after the cell divides many times. Inside cells, most of the DNA is wrapped tightly around proteins called histones. To activate – or transcribe – a gene, the DNA must be re-packaged to allow better access for specific proteins including the enzyme called RNA polymerase II. This repackaging involves a number of changes including chemical modification of the histone proteins. Genes that have been previously transcribed under stress are packaged in a different way so that they are poised and ready for the next time they are needed. However, the details of this process were not clear. Using yeast as a model, D'Urso et al. have dissected the changes that are responsible for priming genes to respond to future events. The yeast gene INO1, which shows transcriptional memory, was studied in cells by characterizing the proteins bound at and around the gene and the histone modifications in the region. D'Urso et al. found that a protein called SfI1 bound to this gene only during transcriptional memory and that this binding was critical to start the phenomenon. Further experiments showed that transcriptional memory also required altering two protein complexes that normally bind to genes when they are switched on. One complex, which includes an enzyme that modifies histones, was altered so that the histones at the INO1 gene were marked in a unique way. The other complex was responsible for recruiting an inactive, poised form of RNA polymerase II to the gene, which allowed the gene to be activated when needed. In addition, D'Urso found that other genes that show transcriptional memory in yeast, as well as such genes in human cells, were also marked in the same ways. A future challenge will be to understand how different conditions in different organisms can lead to transcriptional memory. Further studies could also explore how this memory phenomenon is inherited and how it influences an organism’s fitness.
Institutions: Northwestern University, Northwestern University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2985474303