TY - JOUR
T1 - Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development
AU - Norio, Paolo
AU - Kosiyatrakul, Settapong
AU - Yang, Qiaoxin
AU - Guan, Zeqiang
AU - Brown, Nicholas M.
AU - Thomas, Sharon
AU - Riblet, Roy
AU - Schildkraut, Carl L.
N1 - Funding Information:
We thank B. Birshtein and M. Aladjem for critically reading the manuscript; F. Alt, D. Bastia, D. Gilbert, and C. Newlon for helpful discussions; K. Calame and K. Johnson for advice on the preparation of pro-B cells from the bone marrow; K. Georgopoulos for the TU5 cell line; and S. Shenoy and the A.E.C.O.M. Analytical Imaging and FACS Core Facilities for technical support. This work was supported by the National Institutes of Health (NIH) grants GM45751 (C.L.S.) and AI23548 (R.R.), Immunology and Immunooncology Training Program grant T32CA09173 (S.T.), and by the Cancer Center Support Grant NIH/National Cancer Institute P30CA13330.
PY - 2005/11/23
Y1 - 2005/11/23
N2 - 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).
AB - 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).
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U2 - 10.1016/j.molcel.2005.10.029
DO - 10.1016/j.molcel.2005.10.029
M3 - Article
C2 - 16307921
AN - SCOPUS:27944452746
SN - 1097-2765
VL - 20
SP - 575
EP - 587
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -