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Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer.

Publication ,  Journal Article
Balmelle, N; Zamarreño, N; Krangel, MS; Hernández-Munain, C
Published in: J Immunol
October 15, 2004

The TCR delta enhancer (Edelta) and TCR alpha enhancer (Ealpha) play critical roles in the temporal and lineage-specific control of V(D)J recombination and transcription at the TCR alphadelta locus, working as a developmental switch controlling a transition from TCR delta to TCR alpha activity during thymocyte development. Previous experiments using a transgenic reporter substrate revealed that substitution of the 116-bp minimal Ealpha, denoted Talpha1-Talpha2, for the entire 1.4-kb Ealpha led to a premature activation of V(D)J recombination. This suggested that binding sites outside of Talpha1-Talpha2 are critical for the strict developmental regulation of TCR alpha rearrangement. We have further analyzed Ealpha to better understand the mechanisms responsible for appropriate developmental regulation in vivo. We found that a 275-bp Ealpha fragment, denoted Talpha1-Talpha4, contains all binding sites required for proper developmental regulation in vivo. This suggests that developmentally appropriate enhancer activation results from a functional interaction between factors bound to Talpha1-Talpha2 and Talpha3-Talpha4. In support of this, EMSAs reveal the formation of a large enhanceosome complex that reflects the cooperative assembly of proteins bound to both Talpha1-Talpha2 and Talpha3-Talpha4. Our data suggest that enhanceosome assembly is critical for developmentally appropriate activation of Ealpha in vivo, and that transcription factors, Sp1 and pCREB, may play unique roles in this process.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

October 15, 2004

Volume

173

Issue

8

Start / End Page

5054 / 5063

Location

United States

Related Subject Headings

  • Transcription Factors
  • T-Lymphocytes
  • Recombination, Genetic
  • Phosphorylation
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Genes, T-Cell Receptor alpha
  • Gene Rearrangement
 

Citation

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Balmelle, N., Zamarreño, N., Krangel, M. S., & Hernández-Munain, C. (2004). Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol, 173(8), 5054–5063. https://doi.org/10.4049/jimmunol.173.8.5054
Balmelle, Nadège, Noelia Zamarreño, Michael S. Krangel, and Cristina Hernández-Munain. “Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer.J Immunol 173, no. 8 (October 15, 2004): 5054–63. https://doi.org/10.4049/jimmunol.173.8.5054.
Balmelle N, Zamarreño N, Krangel MS, Hernández-Munain C. Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol. 2004 Oct 15;173(8):5054–63.
Balmelle, Nadège, et al. “Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer.J Immunol, vol. 173, no. 8, Oct. 2004, pp. 5054–63. Pubmed, doi:10.4049/jimmunol.173.8.5054.
Balmelle N, Zamarreño N, Krangel MS, Hernández-Munain C. Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol. 2004 Oct 15;173(8):5054–5063.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

October 15, 2004

Volume

173

Issue

8

Start / End Page

5054 / 5063

Location

United States

Related Subject Headings

  • Transcription Factors
  • T-Lymphocytes
  • Recombination, Genetic
  • Phosphorylation
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Genes, T-Cell Receptor alpha
  • Gene Rearrangement