title: Decreased replication origin activity in temporal transition regions.
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.
authors: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. zguan@aecom.yu.edu
authors: Zeqiang
authors: Z
authors: Guan
authors: Christina M
authors: CM
authors: Hughes
authors: Settapong
authors: S
authors: Kosiyatrakul
authors: Paolo
authors: P
authors: Norio
authors: Ranjan
authors: R
authors: Sen
authors: Steven
authors: S
authors: Fiering
authors: C David
authors: CD
authors: Allis
authors: Eric E
authors: EE
authors: Bouhassira
authors: Carl L
authors: CL
authors: Schildkraut
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000502:physiology*; D053595:Embryonic Stem Cells; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000032:analysis; D018741:Replication Origin; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D007143:Immunoglobulin Heavy Chains; D011993:Recombinant Fusion Proteins