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Transcription orchestrates early DNA replication initiation in mammalian cells

ABSTRACT: DNA replication initiation is spatiotemporally regulated to ensure highly-ordered genome duplication. While it is intriguing to find that DNA replication initiation correlates with actively transcribed regions in mammalian cells, it remains elusive how DNA replication initiation coordinates with transcription. Here we developed a high-resolution method, Nucleoside Analogues Incorporation Loci sequencing (NAIL-seq), to map early replication initiation zones (ERIZs). We found that ERIZs fall into non-transcribed regions of open chromatin compartments, mutually exclusive with transcription. Transcription blockage leads to the ERIZ signals, along with the replicative helicase MCM (mini-chromosome maintenance), infiltrating into active gene bodies. Moreover, pervasive transcription read-through shapes early DNA replication by placing them further downstream. Transcription barriers such as loop anchors and nuclease-dead Cas9 routinely facilitate DNA replication initiation. Therefore we propose a “transcription-dozer” model that transcription orchestrates DNA replication initiation via transcription-mediated redistribution of MCM to transcription-poor regions to avoid replication initiation-transcription collision.

TISSUE(S): Cell Line

SUBMITTER: Chen,Ai

PROVIDER: OEX002082 | NODE |

REPOSITORIES: NODE

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Transcription orchestrates early DNA replication initiation in mammalian cells

Project description:DNA replication initiation is spatiotemporally regulated to ensure highly-ordered genome duplication. While it is intriguing to find that DNA replication initiation correlates with actively transcribed regions in mammalian cells, it remains elusive how DNA replication initiation coordinates with transcription. Here we developed a high-resolution method, Nucleoside Analogues Incorporation Loci sequencing (NAIL-seq), to map early replication initiation zones (ERIZs). We found that ERIZs fall into non-transcribed regions of open chromatin compartments, mutually exclusive with transcription. Transcription blockage leads to the ERIZ signals, along with the replicative helicase MCM (mini-chromosome maintenance), infiltrating into active gene bodies. Moreover, pervasive transcription read-through shapes early DNA replication by placing them further downstream. Transcription barriers such as loop anchors and nuclease-dead Cas9 routinely facilitate DNA replication initiation. Therefore we propose a “transcription-dozer” model that transcription orchestrates DNA replication initiation via transcription-mediated redistribution of MCM to transcription-poor regions to avoid replication initiation-transcription collision.

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