Regulation of DNA replication within the immunoglobulin heavy-chain locus during B cell commitment.

ABSTRACT: The temporal order of replication of mammalian chromosomes appears to be linked to their functional organization, but the process that establishes and modifies this order during cell differentiation remains largely unknown. Here, we studied how the replication of the Igh locus initiates, progresses, and terminates in bone marrow pro-B cells undergoing B cell commitment. We show that many aspects of DNA replication can be quantitatively explained by a mechanism involving the stochastic firing of origins (across the S phase and the Igh locus) and extensive variations in their firing rate (along the locus). The firing rate of origins shows a high degree of coordination across Igh domains that span tens to hundreds of kilobases, a phenomenon not observed in simple eukaryotes. Differences in do

SUBMITTER: Demczuk A 

PROVIDER: S-EPMC3393677 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature