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PMID: 1371250 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication.

The EMBO journal ·Vol. 11 ·No. 1 ·1992-01-00 ·Pages 315-25

Hsieh CL, Lieber MR

Abstract

The physical parameters controlling the accessibility of antigen receptor loci to the V(D)J recombination activity are unknown. We have used minichromosome substrates to study the role that CpG methylation might play in controlling V(D)J recombination site accessibility. We find that CpG methylation decreases the V(D)J recombination of these substrates more than 100-fold. The decrease correlates with a considerable increase in resistance to endonuclease digestion of the methylated minichromosome DNA. The minichromosomes acquire resistance to both the intracellular V(D)J recombinase and exogenous endonuclease only after DNA replication. Therefore, CpG methylation specifies a chromatin structure that, upon DNA replication, is resistant to eukaryotic site-specific recombination. These findings are important to V(D)J recombination as well as to the chromatin assembly of methylated DNA during replication.

MeSH Terms
Animals Cell Line, Transformed Chromatin/metabolism,ultrastructure Chromosome Mapping Chromosomes/metabolism DNA Replication DNA-Cytosine Methylases/metabolism Deoxyribonuclease HpaII Deoxyribonucleases, Type II Site-Specific/metabolism Gene Expression Regulation, Viral Genetic Variation Mice Models, Genetic Polyomavirus/metabolism Receptors, Antigen/genetics Recombination, Genetic
Chemicals
Chromatin Receptors, Antigen DNA-Cytosine Methylases Deoxyribonuclease HpaII Deoxyribonucleases, Type II Site-Specific
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hsieh C L
Department of Pathology, Stanford University School of Medicine, CA 94305-5324.
Lieber M R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-01-00
Pages
315-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC556452
Subset
IM
Grants
NCI NIH HHS · CA51105 · United States
NIGMS NIH HHS · GM43236 · United States
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