Skip to main content

Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2.

Publication ,  Journal Article
Lauzurica, P; Zhong, XP; Krangel, MS; Roberts, JL
Published in: J Exp Med
April 7, 1997

We have analyzed transgenic mice carrying versions of a human T cell receptor (TCR)-delta gene minilocus to study the developmental control of VDJ (variable/diversity/joining) recombination. Previous data indicated that a 1.4-kb DNA fragment carrying the TCR-delta enhancer (E(delta)) efficiently activates minilocus VDJ recombination in vivo. We tested whether the transcription factor CBF/PEBP2 plays an important role in the ability of E(delta) to activate VDJ recombination by analyzing VDJ recombination in mice carrying a minilocus in which the deltaE3 element of E(delta) includes a mutated CBF/PEBP2 binding site. The enhancer-dependent VD to J step of minilocus rearrangement was dramatically inhibited in three of four transgenic lines, arguing that the binding of CBF/PEBP2 plays a role in modulating local accessibility to the VDJ recombinase in vivo. Because mutation of the deltaE3 binding site for the transcription factor c-Myb had previously established a similar role for c-Myb, and because a 60-bp fragment of E(delta) carrying deltaE3 and deltaE4 binding sites for CBF/PEBP2, c-Myb, and GATA-3 displays significant enhancer activity in transient transfection experiments, we tested whether this fragment of E(delta) is sufficient to activate VDJ recombination in vivo. This fragment failed to efficiently activate the enhancer-dependent VD to J step of minilocus rearrangement in all three transgenic lines examined, indicating that the binding of CBF/PEBP2 and c-Myb to their cognate sites within E(delta), although necessary, is not sufficient for the activation of VDJ recombination by E(delta). These results imply that CBF/PEBP2 and c-Myb collaborate with additional factors that bind elsewhere within E(delta) to modulate local accessibility to the VDJ recombinase in vivo.

Duke Scholars

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 7, 1997

Volume

185

Issue

7

Start / End Page

1193 / 1201

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor AP-2
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
  • Gene Expression Regulation, Developmental
  • DNA-Binding Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lauzurica, P., Zhong, X. P., Krangel, M. S., & Roberts, J. L. (1997). Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. J Exp Med, 185(7), 1193–1201. https://doi.org/10.1084/jem.185.7.1193
Lauzurica, P., X. P. Zhong, M. S. Krangel, and J. L. Roberts. “Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2.J Exp Med 185, no. 7 (April 7, 1997): 1193–1201. https://doi.org/10.1084/jem.185.7.1193.
Lauzurica P, Zhong XP, Krangel MS, Roberts JL. Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. J Exp Med. 1997 Apr 7;185(7):1193–201.
Lauzurica, P., et al. “Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2.J Exp Med, vol. 185, no. 7, Apr. 1997, pp. 1193–201. Pubmed, doi:10.1084/jem.185.7.1193.
Lauzurica P, Zhong XP, Krangel MS, Roberts JL. Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. J Exp Med. 1997 Apr 7;185(7):1193–1201.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

April 7, 1997

Volume

185

Issue

7

Start / End Page

1193 / 1201

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor AP-2
  • Receptors, Antigen, T-Cell, gamma-delta
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
  • Gene Expression Regulation, Developmental
  • DNA-Binding Proteins