The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line ε RNA promoter

Jinny Kim, Ray Reeves, Paul B Rothman, Mark Boothby

Research output: Contribution to journalArticle

Abstract

The rate of germ-line RNA transcription correlates with the rate of immunoglobulin heavy chain isotype switching. A promoter element for the transcription of RNA from the germ-line mouse immunoglobulin ε heavy chain constant region gene is induced by interleukin(IL)-4 and lipopolysaccharide, and is bound at its transcription initiation sites by an IL-4-inducible nuclear protein, NF-BRE. To examine the function of the binding site for this IL-4-inducible complex, substitution mutations were introduced in the promoter. These binding site mutations increased promoter activity and decreased binding of NF-BRE. To investigate the paradox of an IL-4-inducible protein binding to a repressor site in an IL-4-inducible promoter, we determined that the non-histone chromosomal protein HMG-I(Y) binds at the transcription initiation sites of the germ-line epsilon promoter. Assays with antisera against HMG-I(Y) revealed monomeric HMG-I(Y) in nuclear extracts. Cotransfection of an expression construct directing the synthesis of anti-sense HMG-I(Y) RNA also increased promoter activity, consistent with a repressor function of HMG-I(Y). Thus, the data are most consistent with a model in which HMG-I(Y) participates in repression of promoter activity. The effects of IL-4 may include derepression at this site.

Original languageEnglish (US)
Pages (from-to)798-808
Number of pages11
JournalEuropean Journal of Immunology
Volume25
Issue number3
StatePublished - Mar 1995
Externally publishedYes

Fingerprint

Non Histone Chromosomal Proteins
Immunoglobulin Heavy Chains
Germ Cells
Interleukin-4
RNA
Transcription Initiation Site
Binding Sites
Immunoglobulin Class Switching
Mutation
Nuclear Proteins
Protein Binding
Lipopolysaccharides
Immune Sera

Keywords

  • Gene transcription
  • Germ-line Ig promoters
  • HMG-I(Y)
  • IgE switch regulation
  • Interleukin-4

ASJC Scopus subject areas

  • Immunology

Cite this

The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line ε RNA promoter. / Kim, Jinny; Reeves, Ray; Rothman, Paul B; Boothby, Mark.

In: European Journal of Immunology, Vol. 25, No. 3, 03.1995, p. 798-808.

Research output: Contribution to journalArticle

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AB - The rate of germ-line RNA transcription correlates with the rate of immunoglobulin heavy chain isotype switching. A promoter element for the transcription of RNA from the germ-line mouse immunoglobulin ε heavy chain constant region gene is induced by interleukin(IL)-4 and lipopolysaccharide, and is bound at its transcription initiation sites by an IL-4-inducible nuclear protein, NF-BRE. To examine the function of the binding site for this IL-4-inducible complex, substitution mutations were introduced in the promoter. These binding site mutations increased promoter activity and decreased binding of NF-BRE. To investigate the paradox of an IL-4-inducible protein binding to a repressor site in an IL-4-inducible promoter, we determined that the non-histone chromosomal protein HMG-I(Y) binds at the transcription initiation sites of the germ-line epsilon promoter. Assays with antisera against HMG-I(Y) revealed monomeric HMG-I(Y) in nuclear extracts. Cotransfection of an expression construct directing the synthesis of anti-sense HMG-I(Y) RNA also increased promoter activity, consistent with a repressor function of HMG-I(Y). Thus, the data are most consistent with a model in which HMG-I(Y) participates in repression of promoter activity. The effects of IL-4 may include derepression at this site.

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