Collisions of RNA polymerases behind the replication fork promote alternative RNA splicing in newly replicated chromatin

DNA replication produces a global disorganization of chromatin structure that takes hours to be restored. However, how these chromatin rearrangements affect the regulation of gene expression and the maintenance of cell identity is not clear. Here, we use ChOR-seq and ChrRNA-seq experiments to analyz...

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Detalles Bibliográficos
Autores: Bruno, Federica, Coronel-Guisado, Cristóbal, González-Aguilera, Cristina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/355421
Acceso en línea:http://hdl.handle.net/10261/355421
https://api.elsevier.com/content/abstract/scopus_id/85182015442
Access Level:acceso abierto
Palabra clave:ChOR-seq
RNAPII
Cell division
Cell identity
Chromatin
Gene expression
Replication
Splicing
Transcription
Transcription-replication conflicts
Descripción
Sumario:DNA replication produces a global disorganization of chromatin structure that takes hours to be restored. However, how these chromatin rearrangements affect the regulation of gene expression and the maintenance of cell identity is not clear. Here, we use ChOR-seq and ChrRNA-seq experiments to analyze RNA polymerase II (RNAPII) activity and nascent RNA synthesis during the first hours after chromatin replication in human cells. We observe that transcription elongation is rapidly reactivated in nascent chromatin but that RNAPII abundance and distribution are altered, producing heterogeneous changes in RNA synthesis. Moreover, this first wave of transcription results in RNAPII blockages behind the replication fork, leading to changes in alternative splicing. Altogether, our results deepen our understanding of how transcriptional programs are regulated during cell division and uncover molecular mechanisms that explain why chromatin replication is an important source of gene expression variability.