Induced transcription in a gene desert region advanced replication timing

To isolate the effect of transcription from native chromatin context, we established an inducible transcription system within a large late-replicating gene desert on mouse chromosome 2. Using Repli-seq, we found that induced transcription is sufficient to advance replication timing across an approximately 800-kb genomic domain.

The induced early-replicating domain displayed an asymmetric replication timing profile relative to the knock-in site, and this asymmetry was independent of transcriptional direction. Genome-wide analysis further showed that pronounced asymmetry is uncommon among native early-replicating domains. These data provide direct evidence that transcription can reshape large-scale replication timing.