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High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

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  • John Mouaikel, CNRS-UPR 3404, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, France
  • Sébastien Z Causse, Institut de Biologie de l'ENS, IBENS, France
  • Mathieu Rougemaille, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, CNRS-UPR 3404, France
  • Yves Daubenton-Carafa, CNRS-UPR 3404, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, France
  • Corinne Blugeon, Institut de Biologie de l'ENS, IBENS, France
  • Sophie Lemoine, Institut de Biologie de l'ENS, IBENS, France
  • Frédéric Devaux, CNRS/UPMC UMR 7238, France
  • Xavier Darzacq, Institut de Biologie de l'ENS, IBENS, France
  • Domenico Libri, CNRS-UPR 3404, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, France
The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence insitu hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the THO complex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation
Original languageEnglish
JournalCell Reports
Volume5
Issue4
Pages (from-to)1082-1094
Number of pages13
DOIs
Publication statusPublished - 27 Nov 2013

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