Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development

Paolo Norio, Settapong Kosiyatrakul, Qiaoxin Yang, Zeqiang Guan, Nicholas M. Brown, Sharon Thomas, Roy Riblet, Carl L. Schildkraut

Research output: Contribution to journalArticle

140 Scopus citations


In mammalian cells, the replication of tissue-specific gene loci is believed to be under developmental control. Here, we provide direct evidence of the existence of developmentally regulated origins of replication in both cell lines and primary cells. By using single-molecule analysis of replicated DNA (SMARD), we identified various groups of coregulated origins that are activated within the Igh locus. These origin clusters can span hundreds of kilobases and are activated sequentially during B cell development, concomitantly with developmentally regulated changes in chromatin structure and transcriptional activity. Finally, we show that the changes in DNA replication initiation that take place during B cell development, within the D-J-C-3′RR region, occur on both alleles (expressed and nonexpressed).

Original languageEnglish (US)
Pages (from-to)575-587
Number of pages13
JournalMolecular Cell
Issue number4
Publication statusPublished - Nov 23 2005


ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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