Role of BSAP in the regulation of human epsilon germ line transcription

L. De Monte, C. P. Thienes, S. Monticelli, H. J. Gould, Donata Vercelli

Research output: Contribution to journalArticle

Abstract

Ig isotype switching in B lymphocytes is directed by cytokines, which activate transcription of the target gene in germ line configuration. Germ line transcripts (GLT) contain short I exons spliced to the heavy chain codons. Expression of GLT is regulated by nuclear factors that bind the I exon promoter and adjacent regions. IL-4 induces epsilon GLT in murine and human B cells. A major IL-4 responsive element (IL-4RE) has been identified upstream of the human I epsilon exon. A Xmal-BclI fragment downstream of the IL-4RE is highly conserved, and contains a site that has been shown to bind the B cell-specific factor BSAP (Pax5) in the mouse. BSAP has been implicated in the regulation of murine epsilon GLT, and in the negative regulation of the Ig 3′ enhancer We have identified a human EBV-negative B cell line, BJAB, that expresses epsilon GLT upon IL-4 stimulation. EMSA analysis with nuclear extracts from unstimulated and IL-4-stimulated BJAB cells has shown that: a) The human epsilon GLT promoter binds BSAP. b) BSAP activity is constitutively expressed in BJAB cells, and in normal peripheral blood B cells. IL-4 does not seem to affect human BSAP binding activity, c) The invariant C in the BSAP binding site is essential for DNA/protein interactions. In order to test the role of BSAP in the IL-4-dependent induction of epsilon GLT, we are currently testing the effects of deletions and/or point mutations in the BSAP binding site in reporter assays.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

Transcription
Germ Cells
Interleukin-4
interleukin-4
germ cells
transcription (genetics)
B-lymphocytes
B-Lymphocytes
Cells
Exons
exons
binding sites
Binding Sites
NFI Transcription Factors
mice
promoter regions
Immunoglobulin Class Switching
Lymphocytes
Sequence Deletion
point mutation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

De Monte, L., Thienes, C. P., Monticelli, S., Gould, H. J., & Vercelli, D. (1996). Role of BSAP in the regulation of human epsilon germ line transcription. FASEB Journal, 10(6).

Role of BSAP in the regulation of human epsilon germ line transcription. / De Monte, L.; Thienes, C. P.; Monticelli, S.; Gould, H. J.; Vercelli, Donata.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

De Monte, L, Thienes, CP, Monticelli, S, Gould, HJ & Vercelli, D 1996, 'Role of BSAP in the regulation of human epsilon germ line transcription', FASEB Journal, vol. 10, no. 6.
De Monte, L. ; Thienes, C. P. ; Monticelli, S. ; Gould, H. J. ; Vercelli, Donata. / Role of BSAP in the regulation of human epsilon germ line transcription. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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