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Status |
Public on May 29, 2024 |
Title |
Polycomb sustains promoters in a deep OFF-state by limiting PIC formation to counteract transcription |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The Polycomb system plays fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here we employ rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking to uncover how the Polycomb system controls transcription in single cells. We discover that the Polycomb system is not a constitutive block to transcription but instead sustains a long-lived deep promoter OFF-state which limits the frequency with which the promoter can enter into a transcribing state. We demonstrate that Polycomb sustains this deep promoter OFF-state by counteracting the binding of factors that enable early transcription pre-initiation complex formation and show that this is necessary for gene repression. Together these important discoveries provide a new rationale for how the Polycomb system controls transcription and suggests a universal mechanism that could enable the Polycomb system to constrain transcription across diverse cellular contexts.
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Overall design |
The genomic distribution of TAF1-T7 was profiled in RING1B-miniAID;TAF1-T7-dTAG mESCs, in which RING1B can be conditionally depleted.
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Contributor(s) |
Szczurek A, Dimitrova E, Klose RJ |
Citation missing |
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Submission date |
Oct 26, 2022 |
Last update date |
May 30, 2024 |
Contact name |
Emilia Dimitrova |
E-mail(s) |
emilia.dimitrova@bioch.ox.ac.uk
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Organization name |
University of Oxford
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Department |
Biochemistry
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Lab |
Rob Klose
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Street address |
South Parks Road
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City |
Oxford |
ZIP/Postal code |
OX1 3QU |
Country |
United Kingdom |
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Platforms (1) |
GPL19415 |
Illumina NextSeq 500 (Homo sapiens; Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA894545 |