Regulation of the replication of the murine immunoglobulin heavy chain gene locus

Evaluation of the role of the 3' regulatory region

Jennifer S. Michaelson, Olga Ermakova, Barbara K. Birshtein, Nasrin Ashouian, Christophe Chevillard, Roy Riblet, Carl L. Schildkraut

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

DNA replication in mammalian cells is a precisely controlled physical and temporal process, likely involving cis-acting elements that control the region(s) from which replication initiates. In B cells, previous studies showed replication timing to be early throughout the immunoglobulin heavy chain (Igh) locus. The implication from replication timing studies in the B- cell line MPC11 was that early replication of the Igh locus was regulated by sequences downstream of the Cα gene. A potential candidate for these replication control sequences was the 3' regulatory region of the Igh locus. Our results demonstrate, however, that the Igh locus maintains early replication in a B-cell line in which the 3' regulatory region has been deleted from one allele, thus indicating that replication timing of the locus is independent of this region. In non-B cells (murine erythroleukemia cells [MEL]), previous studies of segments within the mouse Igh locus demonstrated that DNA replication likely initiated downstream of the Igh gene cluster. Here we use recently cloned DNA to demonstrate that segments located sequentially downstream of the Igh 3' regulatory region continue to replicate progressively earlier in S phase in MEL. Furthermore, analysis by two- dimensional gel electrophoresis indicates that replication forks proceed exclusively in the 3'-to-5' direction through the region 3' of the Igh locus. Extrapolation from these data predicts that initiation of DNA replication occurs in MEL at one or more sites within a 90-kb interval located between 40 and 130 kb downstream of the 3' regulatory region.

Original languageEnglish (US)
Pages (from-to)6167-6174
Number of pages8
JournalMolecular and Cellular Biology
Volume17
Issue number10
StatePublished - Oct 1997

Fingerprint

Immunoglobulin Heavy Chain Genes
Immunoglobulin Heavy Chains
Nucleic Acid Regulatory Sequences
Leukemia, Erythroblastic, Acute
DNA Replication
B-Lymphocytes
Physical Phenomena
Cell Line
Electrophoresis, Gel, Two-Dimensional
Multigene Family
S Phase
Alleles
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Regulation of the replication of the murine immunoglobulin heavy chain gene locus : Evaluation of the role of the 3' regulatory region. / Michaelson, Jennifer S.; Ermakova, Olga; Birshtein, Barbara K.; Ashouian, Nasrin; Chevillard, Christophe; Riblet, Roy; Schildkraut, Carl L.

In: Molecular and Cellular Biology, Vol. 17, No. 10, 10.1997, p. 6167-6174.

Research output: Contribution to journalArticle

Michaelson, JS, Ermakova, O, Birshtein, BK, Ashouian, N, Chevillard, C, Riblet, R & Schildkraut, CL 1997, 'Regulation of the replication of the murine immunoglobulin heavy chain gene locus: Evaluation of the role of the 3' regulatory region', Molecular and Cellular Biology, vol. 17, no. 10, pp. 6167-6174.
Michaelson JS, Ermakova O, Birshtein BK, Ashouian N, Chevillard C, Riblet R et al. Regulation of the replication of the murine immunoglobulin heavy chain gene locus: Evaluation of the role of the 3' regulatory region. Molecular and Cellular Biology. 1997 Oct;17(10):6167-6174.
Michaelson, Jennifer S. ; Ermakova, Olga ; Birshtein, Barbara K. ; Ashouian, Nasrin ; Chevillard, Christophe ; Riblet, Roy ; Schildkraut, Carl L. / Regulation of the replication of the murine immunoglobulin heavy chain gene locus : Evaluation of the role of the 3' regulatory region. In: Molecular and Cellular Biology. 1997 ; Vol. 17, No. 10. pp. 6167-6174.
@article{55a47eea33fd40fd8a68de059d535b28,
title = "Regulation of the replication of the murine immunoglobulin heavy chain gene locus: Evaluation of the role of the 3' regulatory region",
abstract = "DNA replication in mammalian cells is a precisely controlled physical and temporal process, likely involving cis-acting elements that control the region(s) from which replication initiates. In B cells, previous studies showed replication timing to be early throughout the immunoglobulin heavy chain (Igh) locus. The implication from replication timing studies in the B- cell line MPC11 was that early replication of the Igh locus was regulated by sequences downstream of the Cα gene. A potential candidate for these replication control sequences was the 3' regulatory region of the Igh locus. Our results demonstrate, however, that the Igh locus maintains early replication in a B-cell line in which the 3' regulatory region has been deleted from one allele, thus indicating that replication timing of the locus is independent of this region. In non-B cells (murine erythroleukemia cells [MEL]), previous studies of segments within the mouse Igh locus demonstrated that DNA replication likely initiated downstream of the Igh gene cluster. Here we use recently cloned DNA to demonstrate that segments located sequentially downstream of the Igh 3' regulatory region continue to replicate progressively earlier in S phase in MEL. Furthermore, analysis by two- dimensional gel electrophoresis indicates that replication forks proceed exclusively in the 3'-to-5' direction through the region 3' of the Igh locus. Extrapolation from these data predicts that initiation of DNA replication occurs in MEL at one or more sites within a 90-kb interval located between 40 and 130 kb downstream of the 3' regulatory region.",
author = "Michaelson, {Jennifer S.} and Olga Ermakova and Birshtein, {Barbara K.} and Nasrin Ashouian and Christophe Chevillard and Roy Riblet and Schildkraut, {Carl L.}",
year = "1997",
month = "10",
language = "English (US)",
volume = "17",
pages = "6167--6174",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Regulation of the replication of the murine immunoglobulin heavy chain gene locus

T2 - Evaluation of the role of the 3' regulatory region

AU - Michaelson, Jennifer S.

AU - Ermakova, Olga

AU - Birshtein, Barbara K.

AU - Ashouian, Nasrin

AU - Chevillard, Christophe

AU - Riblet, Roy

AU - Schildkraut, Carl L.

PY - 1997/10

Y1 - 1997/10

N2 - DNA replication in mammalian cells is a precisely controlled physical and temporal process, likely involving cis-acting elements that control the region(s) from which replication initiates. In B cells, previous studies showed replication timing to be early throughout the immunoglobulin heavy chain (Igh) locus. The implication from replication timing studies in the B- cell line MPC11 was that early replication of the Igh locus was regulated by sequences downstream of the Cα gene. A potential candidate for these replication control sequences was the 3' regulatory region of the Igh locus. Our results demonstrate, however, that the Igh locus maintains early replication in a B-cell line in which the 3' regulatory region has been deleted from one allele, thus indicating that replication timing of the locus is independent of this region. In non-B cells (murine erythroleukemia cells [MEL]), previous studies of segments within the mouse Igh locus demonstrated that DNA replication likely initiated downstream of the Igh gene cluster. Here we use recently cloned DNA to demonstrate that segments located sequentially downstream of the Igh 3' regulatory region continue to replicate progressively earlier in S phase in MEL. Furthermore, analysis by two- dimensional gel electrophoresis indicates that replication forks proceed exclusively in the 3'-to-5' direction through the region 3' of the Igh locus. Extrapolation from these data predicts that initiation of DNA replication occurs in MEL at one or more sites within a 90-kb interval located between 40 and 130 kb downstream of the 3' regulatory region.

AB - DNA replication in mammalian cells is a precisely controlled physical and temporal process, likely involving cis-acting elements that control the region(s) from which replication initiates. In B cells, previous studies showed replication timing to be early throughout the immunoglobulin heavy chain (Igh) locus. The implication from replication timing studies in the B- cell line MPC11 was that early replication of the Igh locus was regulated by sequences downstream of the Cα gene. A potential candidate for these replication control sequences was the 3' regulatory region of the Igh locus. Our results demonstrate, however, that the Igh locus maintains early replication in a B-cell line in which the 3' regulatory region has been deleted from one allele, thus indicating that replication timing of the locus is independent of this region. In non-B cells (murine erythroleukemia cells [MEL]), previous studies of segments within the mouse Igh locus demonstrated that DNA replication likely initiated downstream of the Igh gene cluster. Here we use recently cloned DNA to demonstrate that segments located sequentially downstream of the Igh 3' regulatory region continue to replicate progressively earlier in S phase in MEL. Furthermore, analysis by two- dimensional gel electrophoresis indicates that replication forks proceed exclusively in the 3'-to-5' direction through the region 3' of the Igh locus. Extrapolation from these data predicts that initiation of DNA replication occurs in MEL at one or more sites within a 90-kb interval located between 40 and 130 kb downstream of the 3' regulatory region.

UR - http://www.scopus.com/inward/record.url?scp=0030840416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030840416&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 6167

EP - 6174

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 10

ER -