TY - JOUR
T1 - Decreased replication origin activity in temporal transition regions
AU - Guan, Zeqiang
AU - Hughes, Christina M.
AU - Kosiyatrakul, Settapong
AU - Norio, Paolo
AU - Sen, Ranjan
AU - Fiering, Steven
AU - Allis, C. David
AU - Bouhassira, Eric E.
AU - Schildkraut, Carl L.
PY - 2009/11/30
Y1 - 2009/11/30
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200905144
DO - 10.1083/jcb.200905144
M3 - Article
C2 - 19951913
AN - SCOPUS:74049163810
SN - 0021-9525
VL - 187
SP - 623
EP - 635
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -