The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription.

Autor: Szczurek AT; Department of Biochemistry, University of Oxford, Oxford, UK. aleksander.szczurek@bioch.ox.ac.uk., Dimitrova E; Department of Biochemistry, University of Oxford, Oxford, UK., Kelley JR; Department of Biochemistry, University of Oxford, Oxford, UK., Blackledge NP; Department of Biochemistry, University of Oxford, Oxford, UK., Klose RJ; Department of Biochemistry, University of Oxford, Oxford, UK. rob.klose@bioch.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Oct; Vol. 26 (10), pp. 1700-1711. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1038/s41556-024-01493-w
Abstrakt: The Polycomb system has fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here, using rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking, we show 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 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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