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 language | English (US) |
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Pages (from-to) | 1387-1414 |
Number of pages | 28 |
Journal | EMBO Reports |
Volume | 25 |
Issue number | 3 |
DOIs | |
State | Published - Mar 12 2024 |
Keywords
- ATP-dependent Chromatin Remodellers
- DNA Repair
- DNA Replication
- Transcription
- Transcription Factor
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics