Apple may have finally thrown the gloves off in the race for larger screens, but it appears that this is old news for cells, who have been elevating the status of important genes for years by marking them with large billboards of H3K4 tri-methylation. These genes then get the VIP treatment from cellular machinery ensuring “enhanced transcriptional consistency.” It’s long been established that H3K4me3 is a mark of active chromatin, located primarily at promoters of actively transcribed genes. Highest enrichment is typically seen within +/- 1kb of the TSS, but a number of recent papers have described genomic locations with broader depositions of H3K4me3 (Adli et al., Aiden et al. and Lien et al. Dr. Anne Brunet’s lab at Stanford set out to investigate the biological relevance of these regions, and here’s what they found:
- Meta-analysis of more than 200 ChIP datasets revealed that the broad H3K4me3 domains were found mostly close to genes, both 5’ and 3’ prime to TSSs, and that these regions varied between cell types.
- The top 5% broadest domains preferentially mark genes that are important for cell identity and function, which were distinct from ‘super-enhancers’, and could be used as a novel tool for identifying regulators in neural progenitor cells.
- These domains exhibit a unique transcriptional regulation of both pol II initiation, elongation and show increased levels of pol II pausing, as well as chromatin accessibility.
- The broad domains are associated with ‘transcriptional consistency’, i.e. a low transcriptional variability, and the authors go on to demonstrate that a reduction to the breadth of the H3K4me3 domain size is associated with a decrease in the transcriptional consistency of the associated genes.
Taken together, the authors propose that these H3K4me3 billboards act as “buffer domains”, where they may help prevent spurious bursts in transcription and ensure that genes important for cellular identity are regulated with surgical precision. Don’t hold your ‘breadth’ any longer, check out the full story here!