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  1. Home
  3. Proximal Termination Generates A Transcriptional State That Determines The Rate Of Establishment Of Polycomb Silencing.
  1. Home
  3. Proximal Termination Generates A Transcriptional State That Determines The Rate Of Establishment Of Polycomb Silencing.

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Proximal termination generates a transcriptional state that determines the rate of establishment of Polycomb

Govind Menon1, Eduardo Mateo-Bonmati2, Svenja Reeck2

  • 1Department of Computational and Systems Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.

Molecular Cell
|June 8, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Polycomb repressive complex 2 (PRC2) silencing establishment is controlled by transcription-coupled repression. Co-transcriptional processing regulates productive transcription, determining the speed of Polycomb repressive complex 2 (PRC2) silencing.

Keywords:
H3K27me3H3K4me1Polycomb silencingalternative polyadenylationanalog and digital gene regulationco-transcriptional processingfeedback interactionsmechanistic mathematical modelingproximal terminationtranscriptional antagonism

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Area of Science:

  • Epigenetics and transcriptional regulation
  • Plant molecular biology
  • Chromatin dynamics

Background:

  • Mechanisms and timescales for de novo chromatin-mediated transcriptional silencing by Polycomb repressive complex 2 (PRC2) remain poorly understood.
  • The FLOWERING LOCUS C (FLC) gene in Arabidopsis serves as a model for studying PRC2 silencing, involving RNA processing, histone demethylation, and PRC2 activity.

Purpose of the Study:

  • To investigate the mechanistic links between co-transcriptional RNA processing, histone modification, and PRC2-mediated transcriptional silencing at the Arabidopsis FLC locus.
  • To develop and validate a computational model explaining how transcription-coupled repression influences the establishment of PRC2 silencing.

Main Methods:

  • Development and testing of a computational model integrating proximal polyadenylation/termination (mediated by FCA), H3K4me1 removal (by FLD), and RNA polymerase II (RNA Pol II) processivity.
  • Experimental validation of model predictions regarding the role of co-transcriptional processing in regulating transcription and PRC2 silencing dynamics.

    • Main Results:

    • A computational model was developed, describing how FCA-mediated termination induces FLD-dependent H3K4me1 removal.
    • H3K4me1 removal was shown to reduce RNA Pol II processivity, enhancing early termination and repressing productive transcription.
    • Model predictions confirmed that transcription-coupled repression levels dictate the timescale for establishing PRC2/H3K27me3 silencing.

    Conclusions:

    • Co-transcriptional RNA processing at the FLC locus sets the level of productive transcription.
    • This level of productive transcription directly influences the rate of the transition to Polycomb repressive complex 2 (PRC2) mediated silencing.
    • The study elucidates a novel feedback mechanism linking RNA processing to chromatin-based transcriptional repression.