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PMID: 2582426 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Specific 5' and 3' regions of the mu-chain gene are undermethylated at distinct stages of B-cell differentiation.

Blackman MA, Koshland ME

Abstract

The mu-chain gene is expressed differently in successive stages of B-lymphocyte development. The heavy chain product appears as a cytoplasmic constituent in pre-B-cells, as part of the IgM receptor in maturing B cells, and as a component in the pentamer IgM antibody synthesized and secreted by the antigen-stimulated cell. We have used the methylation of CpG sequences as an assay system to define the chromatin changes associated with different expression of the mu-chain. The methylation status of eight index sites was followed by restriction enzyme analysis of murine cell lines representing the major stages in the developmental pathway. The analyses showed that a single Msp I/Hpa II site 5' to the immunoglobulin enhancer becomes undermethylated with the onset of mu-chain gene transcription. Four midgene Msp I/Hpa II sites exhibit a progressive loss of methyl groups unrelated to changes in mu-chain gene expression, whereas a Msp I/Hpa II site and two Hha I sites surrounding the exon encoding the carboxyl terminus of the secreted form of mu chain (mus) become undermethylated during the transition to IgM secretion. These results indicate that structural changes in local regions of the mu-chain gene correlate with specific developmental events.

MeSH Terms
B-Lymphocytes/cytology,immunology Base Sequence Cell Differentiation DNA Restriction Enzymes/metabolism Deoxyribonuclease EcoRI Deoxyribonuclease HpaII Gene Expression Regulation Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin mu-Chains/genetics Methylation
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin mu-Chains DNA Restriction Enzymes Deoxyribonuclease EcoRI Deoxyribonuclease HpaII
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Blackman M A
Koshland M E
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37 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1985-06-00
Pages
3809-13
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC397877
Subset
IM
Grants
PHS HHS · A1-07079 · United States
NCI NIH HHS · CA-09179 · United States
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