Regulation of T Cell Receptor β Gene Rearrangements and Allelic Exclusion by the Helix-Loop-Helix Protein, E47

Yasutoshi Agata, Nobuyuki Tamaki, Shuji Sakamoto, Tomokatsu Ikawa, Kyoko Masuda, Hiroshi Kawamoto, Cornelis Murre

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic locus activation upon rearrangement and subsequently by feedback inhibition of continued rearrangement. Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor β (TCRβ) gene rearrangement by directly binding to target gene segments to increase chromatin accessibility in a dosage-sensitive manner. Feedback signaling abrogated E47 binding, leading to a decline in accessibility. Conversely, enforced expression of E47 induced TCRβ gene rearrangement by antagonizing feedback inhibition. Thus, the abundance of E47 is rate limiting in locus activation, and feedback signaling downregulates E47 activity to ensure allelic exclusion.

Original languageEnglish
Pages (from-to)871-884
Number of pages14
JournalImmunity
Volume27
Issue number6
DOIs
Publication statusPublished - 21-12-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Regulation of T Cell Receptor β Gene Rearrangements and Allelic Exclusion by the Helix-Loop-Helix Protein, E47'. Together they form a unique fingerprint.

Cite this