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Regulation of stochastic gene bursting by chromatin-independent acetylation

ABSTRACT: Stochastic transcriptional bursting is a universal property of gene expression. Different genes exhibit distinct bursting patterns, but the molecular mechanisms that determine bursting kinetics are largely unknown. We have developed and applied a high-throughput-imaging based screening strategy to identify cellular factors and mechanisms that determine the bursting behavior of human genes. Focusing on epigenetic regulators, we find that protein acetylation is a strong acute modulator of burst frequency, burst size and heterogeneity of bursting. Acetylation globally affected the Off-time of genes, but had gene-specific effects on the On-time. Yet, these effects were not linked to promoter acetylation, which did not correlate with bursting properties, and forced promoter acetylation had variable effects on bursting. Instead, we identified acetylation of the Integrator complex as a key determinant of gene bursting. Specifically, we find that elevated Integrator acetylation increases bursting. Taken together our results suggest a prominent role of non-histone proteins in determining gene bursting properties, and they point towards histone-independent acetylation of a transcription cofactor as an allosteric modulator of bursting via a pause-release related bursting checkpoint.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Tom Misteli

PROVIDER: MSV000094611 | MassIVE | Wed Apr 24 09:37:00 BST 2024

REPOSITORIES: MassIVE

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Regulation of stochastic gene bursting by chromatin-independent acetylation

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