HoxB domain induction silences DNA replication origins in the locus and specifies a single origin at its boundary

In multicellular organisms, changes in the DNA replication programme could act to integrate differentiation with cell division in various developmental and transcriptional contexts. Here, we have addressed the use of DNA replication origins during differentiation in the HoxB domain—a cluster of nine...

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Veröffentlicht in:EMBO reports 2006-08, Vol.7 (8), p.812-816
Hauptverfasser: Grégoire, Damien, Brodolin, Konstantin, Méchali, Marcel
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Brodolin, Konstantin
Méchali, Marcel
description In multicellular organisms, changes in the DNA replication programme could act to integrate differentiation with cell division in various developmental and transcriptional contexts. Here, we have addressed the use of DNA replication origins during differentiation in the HoxB domain—a cluster of nine genes developmentally regulated in a collinear manner. In undifferentiated mouse P19 cells, we detected several DNA replication origins in the 100 kb HoxB locus, indicating a relaxed origin use when the locus is transcriptionally silent. By contrast, in retinoic‐acid‐induced differentiated cells, when HoxB transcription is activated, a general silencing of DNA replication origins occurs in the locus except one located downstream of Hoxb1 , at the 3′ boundary of the HoxB domain. Silencing of the replication origins is associated with histone hyperacetylation, whereas the active Hoxb1 origin persists as a hypoacetylated island. These findings provide direct evidence for the differentiated use of origins in HoxB genes, and we suggest that this regulation might contribute to the regulated expression of HoxB genes during development.
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source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Acetylation
Animals
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line, Tumor
Chromatin Immunoprecipitation
Deoxyribonucleic acid
DNA
DNA Replication - genetics
Gene expression
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Gene loci
Genetics
Histones - genetics
Histones - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Human genetics
Life Sciences
Models, Genetic
Origin Recognition Complex - genetics
Origin Recognition Complex - metabolism
Prenatal development
Replication Origin - genetics
Rodents
Scientific Report
Scientific Reports
Transcription, Genetic - drug effects
Transcription, Genetic - genetics
Tretinoin - pharmacology
title HoxB domain induction silences DNA replication origins in the locus and specifies a single origin at its boundary
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