RNA polymerase II promotes the organization of chromatin following DNA replication

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Abstract

Understanding how chromatin organisation is duplicated on the two daughter strands is a central question in epigenetics. In mammals, following the passage of the replisome, nucleosomes lose their defined positioning and transcription contributes to their re-organisation. However, whether transcription plays a greater role in the organization of chromatin following DNA replication remains unclear. Here we analysed protein re-association with newly replicated DNA upon inhibition of transcription using iPOND coupled to quantitative mass spectrometry. We show that nucleosome assembly and the re-establishment of most histone modifications are uncoupled from transcription. However, RNAPII acts to promote the re-association of hundreds of proteins with newly replicated chromatin via pathways that are not observed in steady-state chromatin. These include ATP-dependent remodellers, transcription factors and histone methyltransferases. We also identify a set of DNA repair factors that may handle transcription-replication conflicts during normal transcription in human non-transformed cells. Our study reveals that transcription plays a greater role in the organization of chromatin post-replication than previously anticipated.

Original languageEnglish
Pages (from-to)1387-1414
Number of pages28
JournalEMBO Reports
Volume25
Issue number3
Early online date12 Feb 2024
DOIs
Publication statusPublished - 12 Mar 2024

Keywords

  • DNA Replication
  • Transcription
  • ATP-dependent Chromatin Remodellers
  • Transcription Factor
  • DNA Repair

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