Decreased replication origin activity in temporal transition regions

Zeqiang Guan, Christina M. Hughes, Settapong Kosiyatrakul, Paolo Norio, Ranjan Sen, Steven Fiering, C. David Allis, Eric E. Bouhassira, Carl L. Schildkraut

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, and enhancement of local histone modifications characteristic of active chromatin did not lead to origin activation. Moreover, very few replication initiation events were observed when two ectopic replication origin sequences were inserted into the TTR. These findings indicate that the Igh TTR represents a repressive compartment that inhibits replication initiation, thus maintaining the boundaries between early and late replication domains.

Original languageEnglish (US)
Pages (from-to)623-635
Number of pages13
JournalJournal of Cell Biology
Issue number5
StatePublished - Nov 30 2009

ASJC Scopus subject areas

  • Cell Biology


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