Characterization of a novel negative regulatory element in the human interleukin 4 promoter

S. N. Georas, J. Cumberland, T. Burke, E. Park, S. Ono, V. Casolaro

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin 4 (IL-4) is a multifunctional cytokine that plays an important role in hematopoiesis, tumor cell growth, and cellular immune responses. Expression of the IL-4 gene is tightly controlled at the level of gene transcription, and many positive regulatory cis-elements have been identified in the proximal IL-4 promoter region. Relatively little is known about factors that downregulate IL-4 transcription. We performed a detailed deletional analysis of the proximal human IL-4 promoter and studied reporter gene activity in transiently transfected Jurkat T lymphoblasts. In this report, we characterize a novel negative regulatory element (termed P2 NRE) that is adjacent to a binding site for nuclear factor of activated T cells. Mutation of P2 NRE significantly enhanced the activity of a 175 base pair IL-4 promoter construct in transiently transfected Jurkat T lymphoblasts. Using nuclear extracts from Jurkat cells, we identify a candidate factor (termed Rep-1) that binds uniquely to the P2 NRE in DNA-binding assays. Rep-1 is not related to other factors previously shown to interact with the IL-4 promoter, and by UV cross-linking and SDS-PAGE analysis, we found that it migrates with a molecular mass of approximately 150 kDa. Characterizing the molecular mechanisms responsible for downregulating the IL-4 promoter should enhance our understanding of IL-4-gene dysregulation in disease states.

Original languageEnglish (US)
Pages (from-to)629-635
Number of pages7
JournalLeukemia
Volume14
Issue number4
StatePublished - 2000

Keywords

  • Allergy
  • Cytokines
  • Gene regulation
  • Human
  • T lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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