Transcriptional regulation of the human CD3γ gene: The TATA-less CD3γ promoter functions via an initiator and contiguous Sp-binding elements

Bassam M. Badran, Kevin Kunstman, Jennifer Stanton, Maria Moschitta, Anne Zerghe, Haidar Akl, Arsène Burny, Steven M Wolinsky, Karen E. Willard-Gallo*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Growing evidence that the CD3γ gene is specifically targeted in some T cell diseases focused our attention on the need to identify and characterize the elusive elements involved in CD3γ transcriptional control. In this study, we show that while the human CD3γ and CD3δ genes are oriented head-to-head and separated by only 1.6 kb, the CD3γ gene is transcribed from an independent but weak, lymphoid-specific TATA-less proximal promoter. Using RNA ligase-mediated rapid amplification of cDNA ends, we demonstrate that a cluster of transcription initiation sites is present in the vicinity of the primary core promoter, and the major start site is situated in a classical initiator sequence. A GT box immediately upstream of the initiator binds Sp family proteins and the general transcription machinery, with the activity of these adjacent elements enhanced by the presence of a second GC box 10 nt further upstream. The primary core promoter is limited to a sequence that extends upstream to -15 and contains the initiator and GT box. An identical GT box located ∼50 nt from the initiator functions as a weak secondary core promoter and likely generates transcripts originating upstream from the +1. Finally, we show that two previously identified NFAT motifs in the proximal promoter positively (NFATγ1) or negatively (NFATγ 1 and NFATγ2) regulate expression of the human CD3γ gene by their differential binding of NFATc1 plus NF-κB p50 or NFATc2 containing complexes, respectively. These data elucidate some of the mechanisms controlling expression of the CD3γ gene as a step toward furthering our understanding of how its transcription is targeted in human disease.

Original languageEnglish (US)
Pages (from-to)6238-6249
Number of pages12
JournalJournal of Immunology
Volume174
Issue number10
StatePublished - May 15 2005

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Badran, B. M., Kunstman, K., Stanton, J., Moschitta, M., Zerghe, A., Akl, H., Burny, A., Wolinsky, S. M., & Willard-Gallo, K. E. (2005). Transcriptional regulation of the human CD3γ gene: The TATA-less CD3γ promoter functions via an initiator and contiguous Sp-binding elements. Journal of Immunology, 174(10), 6238-6249.