RNA polymerase II promotes the organization of chromatin following DNA replication

TY - JOUR

T1 - RNA polymerase II promotes the organization of chromatin following DNA replication

AU - Bandau, Susanne

AU - Alvarez, Vanesa

AU - Jiang, Hao

AU - Graff, Sarah

AU - Sundaramoorthy, Ramasubramanian

AU - Gierlinski, Marek

AU - Toman, Matt

AU - Owen-Hughes, Tom

AU - Sidoli, Simone

AU - Lamond, Angus

AU - Alabert, Constance

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/3/12

Y1 - 2024/3/12

N2 - 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.

AB - 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.

KW - DNA Replication

KW - Transcription

KW - ATP-dependent Chromatin Remodellers

KW - Transcription Factor

KW - DNA Repair

UR - https://www.scopus.com/pages/publications/85185283017

U2 - 10.1038/s44319-024-00085-x

DO - 10.1038/s44319-024-00085-x

M3 - Article

C2 - 38347224

SN - 1469-221X

VL - 25

SP - 1387

EP - 1414

JO - EMBO Reports

JF - EMBO Reports

IS - 3

ER -