Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development.
In mammalian cells, the replication of tissue-specific gene loci is believed to be under developmental control. Here, we provide direct evidence of the existence of developmentally regulated origins of replication in both cell lines and primary cells. By using single-molecule analysis of replicated DNA (SMARD), we identified various groups of coregulated origins that are activated within the Igh locus. These origin clusters can span hundreds of kilobases and are activated sequentially during B cell development, concomitantly with developmentally regulated changes in chromatin structure and transcriptional activity. Finally, we show that the changes in DNA replication initiation that take place during B cell development, within the D-J-C-3'RR region, occur on both alleles (expressed and nonexpressed).
Norio
Paolo
P
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. norio@aecom.yu.edu
Kosiyatrakul
Settapong
S
Yang
Qiaoxin
Q
Guan
Zeqiang
Z
Brown
Nicholas M
NM
Thomas
Sharon
S
Riblet
Roy
R
Schildkraut
Carl L
CL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004261:DNA Replication / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization; D016196:S Phase / Q000502:physiology; D024363:Transcription Initiation Site / Q000502:physiology*
D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains