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TEA regulates local TCR-Jalpha accessibility through histone acetylation
Laurent Mauvieux1, Isabelle Villey, Jean-Pierre de Villartay
1Développement normal et pathologique du système immunitaire, INSERM U429, Hôpital Necker-Enfants-Malades, Paris, France.
European Journal of Immunology
|July 29, 2003
Summary
The T early alpha element (TEA) controls histone acetylation at specific T-cell receptor alpha (TCRalpha) gene segments. This epigenetic modification enhances DNA accessibility, optimizing TCRalpha usage and boosting immune receptor diversity.
Area of Science:
- Immunology
- Epigenetics
- Molecular Biology
Background:
- Histone acetylation regulates gene accessibility.
- Enhancer elements control locus accessibility.
- T-cell receptor alpha (TCRalpha) locus rearrangement is crucial for T-cell development.
Purpose of the Study:
- To investigate the role of the T early alpha (TEA) element in controlling chromatin acetylation along the TCRalpha locus.
- To determine the impact of TEA on histone modifications and DNA accessibility during T-cell maturation.
Main Methods:
- Targeted deletion of the TEA element in thymocytes.
- Chromatin immunoprecipitation (ChIP) to assess histone acetylation (H3 and H4).
- Analysis of DNA accessibility in relation to TEA and histone acetylation.
Main Results:
- Targeted deletion of TEA abolished histone H3 and H4 acetylation at upstream Jalpha segments.
- Histone acetylation persisted in downstream Jalpha segments despite TEA deletion.
- TEA-dependent acetylation occurred during the immature single-positive stage, coinciding with ValphaJalpha recombination initiation.
- TEA-mediated acetylation enhanced DNA accessibility at upstream Jalpha segments.
Conclusions:
- The TEA element is essential for initiating locus-specific histone acetylation at the TCRalpha locus.
- TEA-dependent epigenetic modifications are critical for optimizing TCRalpha gene rearrangement and enhancing T-cell receptor diversity potential.