Identification of 3′ α-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation

Jennifer S. Michaelson, Sandra L. Giannini, Barbara K. Birshtein

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

In addition to Eμ, several elements downstream of the IgH cluster, i.e. 3′ of the Cα gene, are involved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses ∼34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located -33 kb downstream of the α gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3′α-hs4, is capable of activity through-out B cell development. Transient transfection of 3′α-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of Eμ in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in a pre-B cell line, 18-81, the average activity is 25% that of Eμ. Enhancer activity was localized to an 800 bp fragment. The activity of 3′α-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3′α-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pre B cell line, 18-81.

Original languageEnglish (US)
Pages (from-to)975-981
Number of pages7
JournalNucleic Acids Research
Volume23
Issue number6
StatePublished - Mar 25 1995

Fingerprint

Cell Differentiation
Immunoglobulin Heavy Chains
B Cells
B-Lymphocytes
Cells
Cell Line
B-Lymphoid Precursor Cells
Line
Gene
Genes
Plasmacytoma
Cell
Deletion
Gene Rearrangement
Nucleic Acid Regulatory Sequences
Deoxyribonuclease I
Plasma Cells
Rearrangement
Reporter Genes
Mutant

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)

Cite this

Identification of 3′ α-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation. / Michaelson, Jennifer S.; Giannini, Sandra L.; Birshtein, Barbara K.

In: Nucleic Acids Research, Vol. 23, No. 6, 25.03.1995, p. 975-981.

Research output: Contribution to journalArticle

Michaelson, Jennifer S. ; Giannini, Sandra L. ; Birshtein, Barbara K. / Identification of 3′ α-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation. In: Nucleic Acids Research. 1995 ; Vol. 23, No. 6. pp. 975-981.
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