H3K4me3 breadth is linked to cell identity and transcriptional consistency
By B. Benayoun, E. Pollina, Duygu Ucar, S. Mahmoudi, K. Karra, E. Wong, Keerthana Devarajan, Aaron C. Daugherty, Anshul B Kundaje, E. Mancini and 7 more. Cell, 2014
480 citations recorded by the source corpus.
Summary Trimethylation of Histone H3 at Lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. Broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by broadest H3K4me3 domains exhibit enhanced transcriptional consistency rather than increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/4afbdfbb8dfc7b22fab3d37d2e81166e8a1facea
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In Molecular Biology
Citations in the corpus
- Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism (2015, background): “…methylation modifications on their tails, such as trimethylation at lysine 4, are known to be required for the maintenance of defined cellular states (Benayoun et al., 2014; Ruthenburg et al., 2007) and have been shown to be modulated by metabolism (Shiraki et al., 2014; Shyh-Chang et al., 2013).”