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| Status |
Public on Jun 26, 2024 |
| Title |
Regulation of stochastic gene bursting by chromatin-independent acetylation |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Stochastic transcriptional bursting is now recognized as a universal property of gene expression. While different genes exhibit distinct bursting patterns, the molecular basis for differences in bursting 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 global acetylation is the strongest acute modulator of burst frequency, size and heterogeneity of bursting. Acetylation similarly affected the Off-time but On-time changes were gene-specific. These effects were not strongly linked to promoter acetylation, which did not correlate with bursting properties and forced promoter acetylation altered bursting for only some genes. Instead, we identified acetylation of the Integrator complex as a key determinant of gene bursting with elevated Integrator acetylation leading to faster bursting. Taken together our results suggest a dominant role of non-histone proteins in determining gene bursting properties and they identify non-epigenetic acetylation of a transcription cofactor as an allosteric modulator of bursting via a pause-release related bursting checkpoint
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| Overall design |
Spike in calibrated ChIP-seq for H3K27ac in DMSO and Panobinostat treated HBEC cells
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| Contributor(s) |
Sood V, Larson D, Misteli T |
| Citation(s) |
38903099 |
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| Submission date |
Feb 01, 2024 |
| Last update date |
Jun 27, 2024 |
| Contact name |
Varun Sood |
| E-mail(s) |
varun.sood@nih.gov
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| Phone |
7348342107
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| Organization name |
National Institues of Health, National Cancer Institute, Center for Cancer Research
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| Department |
Laboratory of receptor biology and gene expression
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| Lab |
Misteli
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| Street address |
41 Medlars Drive
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| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20814 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA1072108 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE254866_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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