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 journalArticle

39 Citations (Scopus)

Abstract

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
Volume187
Issue number5
DOIs
StatePublished - Nov 30 2009

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Replication Origin
Temporal Lobe
Immunoglobulin Heavy Chains
Transcriptional Activation
B-Lymphocytes
Histone Code
Embryonic Stem Cells
DNA Replication
Epigenomics
Chromatin
Genome

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Guan, Z., Hughes, C. M., Kosiyatrakul, S., Norio, P., Sen, R., Fiering, S., ... Schildkraut, C. L. (2009). Decreased replication origin activity in temporal transition regions. Journal of Cell Biology, 187(5), 623-635. https://doi.org/10.1083/jcb.200905144

Decreased replication origin activity in temporal transition regions. / Guan, Zeqiang; Hughes, Christina M.; Kosiyatrakul, Settapong; Norio, Paolo; Sen, Ranjan; Fiering, Steven; Allis, C. David; Bouhassira, Eric E.; Schildkraut, Carl L.

In: Journal of Cell Biology, Vol. 187, No. 5, 30.11.2009, p. 623-635.

Research output: Contribution to journalArticle

Guan, Z, Hughes, CM, Kosiyatrakul, S, Norio, P, Sen, R, Fiering, S, Allis, CD, Bouhassira, EE & Schildkraut, CL 2009, 'Decreased replication origin activity in temporal transition regions', Journal of Cell Biology, vol. 187, no. 5, pp. 623-635. https://doi.org/10.1083/jcb.200905144
Guan Z, Hughes CM, Kosiyatrakul S, Norio P, Sen R, Fiering S et al. Decreased replication origin activity in temporal transition regions. Journal of Cell Biology. 2009 Nov 30;187(5):623-635. https://doi.org/10.1083/jcb.200905144
Guan, Zeqiang ; Hughes, Christina M. ; Kosiyatrakul, Settapong ; Norio, Paolo ; Sen, Ranjan ; Fiering, Steven ; Allis, C. David ; Bouhassira, Eric E. ; Schildkraut, Carl L. / Decreased replication origin activity in temporal transition regions. In: Journal of Cell Biology. 2009 ; Vol. 187, No. 5. pp. 623-635.
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