Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters

Nat Immunol. 2005 May;6(5):481-9. doi: 10.1038/ni1189. Epub 2005 Apr 3.

Abstract

Assembly of the gene encoding T cell receptor alpha (Tcra) is characterized by an orderly progression of primary and secondary V(alpha)-to-J(alpha) recombination events across the J(alpha) array, but the targeting mechanisms responsible for this progression are mostly unknown. Studies have shown that the T early-alpha promoter is important in targeting primary Tcra rearrangements. We found that T early-alpha and a previously unknown promoter associated with J(alpha)49 targeted primary recombination to discrete sets of constant alpha region (C(alpha))-distal J(alpha) segments and together directed nearly all normal primary recombination events. Furthermore, deletion of the T early-alpha promoter activated previously suppressed downstream promoters and stimulated primary rearrangement to centrally located J(alpha) segments. Central promoter derepression also occurred after primary rearrangement, thereby providing a mechanism to target secondary recombination events.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • Cell Differentiation
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Gene Expression Regulation / genetics*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / genetics*
  • Germ Cells / metabolism*
  • Histones / metabolism
  • Humans
  • Mice
  • Promoter Regions, Genetic / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Sequence Deletion / genetics
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Transcription, Genetic / genetics

Substances

  • Chromatin
  • Histones
  • Receptors, Antigen, T-Cell, alpha-beta