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Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus.

Publication ,  Journal Article
Sleckman, BP; Carabana, J; Zhong, X; Krangel, MS
Published in: Immunology
September 2001

Although situated close together within the T-cell receptor (TCR) alpha/delta locus, TCR delta and TCR alpha gene segments are controlled by two developmental stage-specific enhancers and are activated according to distinct developmental programmes. We previously used a stable transfection colony assay to identify an enhancer-blocking element, blocking element alpha/delta-1 (BEAD-1), between the TCR delta and alpha gene segments of the human TCR alpha/delta locus. We hypothesized that enhancer-blocking by BEAD-1 might be required to prevent the TCR delta enhancer from activating TCR alpha gene segment transcription and rearrangement at the double negative stage of thymocyte development. Here, we used a transfection approach to define partial enhancer-blocking activity in an analogous position of the murine TCR alpha/delta locus. To test the functional significance of this activity in vivo, we used gene targeting to delete the region from the endogenous locus. We found no perturbation of TCR delta and TCR alpha gene expression and rearrangement on targeted alleles, indicating that enhancer-blocking activity in this region is not required to maintain the developmentally distinct activation profiles of the two genes. We suggest that appropriate regulation may be achieved as a result of intrinsic biases in enhancer-promoter interactions or a developmental stage specificity to promoter function that is distinct from any additional specificity imposed by the enhancers themselves.

Duke Scholars

Published In

Immunology

DOI

ISSN

0019-2805

Publication Date

September 2001

Volume

104

Issue

1

Start / End Page

11 / 18

Location

England

Related Subject Headings

  • Transfection
  • Thymus Gland
  • Spleen
  • Mice, Transgenic
  • Mice
  • Immunology
  • Genes, T-Cell Receptor delta
  • Genes, T-Cell Receptor alpha
  • Gene Targeting
  • Gene Expression Regulation, Developmental
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sleckman, B. P., Carabana, J., Zhong, X., & Krangel, M. S. (2001). Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus. Immunology, 104(1), 11–18. https://doi.org/10.1046/j.1365-2567.2001.01304.x
Sleckman, B. P., J. Carabana, X. Zhong, and M. S. Krangel. “Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus.Immunology 104, no. 1 (September 2001): 11–18. https://doi.org/10.1046/j.1365-2567.2001.01304.x.
Sleckman BP, Carabana J, Zhong X, Krangel MS. Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus. Immunology. 2001 Sep;104(1):11–8.
Sleckman, B. P., et al. “Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus.Immunology, vol. 104, no. 1, Sept. 2001, pp. 11–18. Pubmed, doi:10.1046/j.1365-2567.2001.01304.x.
Sleckman BP, Carabana J, Zhong X, Krangel MS. Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus. Immunology. 2001 Sep;104(1):11–18.

Published In

Immunology

DOI

ISSN

0019-2805

Publication Date

September 2001

Volume

104

Issue

1

Start / End Page

11 / 18

Location

England

Related Subject Headings

  • Transfection
  • Thymus Gland
  • Spleen
  • Mice, Transgenic
  • Mice
  • Immunology
  • Genes, T-Cell Receptor delta
  • Genes, T-Cell Receptor alpha
  • Gene Targeting
  • Gene Expression Regulation, Developmental