Transcriptional regulation of the human polymeric Ig receptor gene: Analysis of basal promoter elements

Paula M. Hempen, Kimberly M. Phillips, Pamela S. Conway, Katrina H. Sandoval, Tracey A. Schneeman, Hsin-Jung Joyce Wu, Charlotte S. Kaetzel

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Secretory Igs provide the first line of adaptive immune defense against ingested, inhaled, and sexually transmitted pathogens at mucosal surfaces. The polymeric Ig receptor regulates transport of dimeric IgA and pentameric IgM into external secretions. The level of expression of polymeric Ig receptor is controlled to a large extent by transcription of the PIGR gene in mucosal epithelial cells. Here we present a detailed analysis of the promoter of the PIGR gene by transient transfection of luciferase reporter plasmids into cultured cell lines. Comparisons of the human and mouse PIGR promoters in human and mouse intestinal and liver cell lines demonstrated that the human PIGR promoter was 4- to 5-fold more active than the mouse PIGR promoter in all cell types, and that both the human and mouse PIGR promoters were more active in intestinal than in liver cell lines. Targeted deletions of 22-bp segments of the human PIGR promoter revealed that the region from nt -63 to -84 is crucial for basal transcription, and that two upstream regions can act as positive or negative regulators. Point mutations within the region from nt -63 to -84 demonstrated that an E box motif, which binds the basic helix-loop-helix protein upstream stimulatory factor, is required for PIGR promoter activity. Two additional regulatory motifs were identified in the proximal promoter region: a binding site for AP2, and an inverted repeat motif that binds an unidentified protein. These findings suggest that cooperative binding of multiple transcription factors regulates basal activity of the human PIGR promoter.

Original languageEnglish (US)
Pages (from-to)1912-1921
Number of pages10
JournalJournal of Immunology
Volume169
Issue number4
StatePublished - Aug 15 2002
Externally publishedYes

Fingerprint

Polymeric Immunoglobulin Receptors
Immunoglobulin Genes
Genetic Promoter Regions
Cell Line
Upstream Stimulatory Factors
E-Box Elements
Liver
Luciferases
Point Mutation
Human Activities
Immunoglobulin A
Genes
Transfection
Immunoglobulin M
Cultured Cells
Proteins
Plasmids
Transcription Factors
Epithelial Cells
Binding Sites

ASJC Scopus subject areas

  • Immunology

Cite this

Hempen, P. M., Phillips, K. M., Conway, P. S., Sandoval, K. H., Schneeman, T. A., Wu, H-J. J., & Kaetzel, C. S. (2002). Transcriptional regulation of the human polymeric Ig receptor gene: Analysis of basal promoter elements. Journal of Immunology, 169(4), 1912-1921.

Transcriptional regulation of the human polymeric Ig receptor gene : Analysis of basal promoter elements. / Hempen, Paula M.; Phillips, Kimberly M.; Conway, Pamela S.; Sandoval, Katrina H.; Schneeman, Tracey A.; Wu, Hsin-Jung Joyce; Kaetzel, Charlotte S.

In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 1912-1921.

Research output: Contribution to journalArticle

Hempen, PM, Phillips, KM, Conway, PS, Sandoval, KH, Schneeman, TA, Wu, H-JJ & Kaetzel, CS 2002, 'Transcriptional regulation of the human polymeric Ig receptor gene: Analysis of basal promoter elements', Journal of Immunology, vol. 169, no. 4, pp. 1912-1921.
Hempen PM, Phillips KM, Conway PS, Sandoval KH, Schneeman TA, Wu H-JJ et al. Transcriptional regulation of the human polymeric Ig receptor gene: Analysis of basal promoter elements. Journal of Immunology. 2002 Aug 15;169(4):1912-1921.
Hempen, Paula M. ; Phillips, Kimberly M. ; Conway, Pamela S. ; Sandoval, Katrina H. ; Schneeman, Tracey A. ; Wu, Hsin-Jung Joyce ; Kaetzel, Charlotte S. / Transcriptional regulation of the human polymeric Ig receptor gene : Analysis of basal promoter elements. In: Journal of Immunology. 2002 ; Vol. 169, No. 4. pp. 1912-1921.
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