Proceedings of the National Academy of Sciences · 2018 · 187 citations · 40 references
Life SciencesBiologyMolecular BiologyCircadian RhythmsGene ExpressionTranscriptional RegulationChromatinCircadian Gene ExpressionHistone ProteinsPromoter RegulationTranscriptional BurstingTranscriptional ControlBurst SizeCell-to-cell VariabilityCircadian Promoter ElementsCircadian Rhythm Gene ExpressionCircadian Transcriptional RegulationHistone AcetylationReporter GenesRhythmic Transcription
transcription. We then found that promoter histone-acetylation level covaried with burst frequency, being greatest at peak expression and lowest at trough expression, while remaining unaffected by the genomic location. In addition, specific deletions of ROR-responsive elements led to constitutively elevated histone acetylation and burst frequency. We then investigated the suggested link between histone acetylation and burst frequency by dCas9p300-targeted modulation of histone acetylation, revealing that acetylation levels influence burst frequency more than burst size. The correlation between acetylation levels at the promoter and burst frequency was also observed in endogenous circadian genes and in embryonic stem cell fate genes. Thus, our data suggest that histone acetylation-mediated control of transcription burst frequency is a common mechanism to control mammalian gene expression.
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