TEA regulates local TCR-Jalpha accessibility through histone acetylation.
Enhancer alpha-dependent histone acetylation has been proposed as a molecular mechanism underlying the control of accessibility of recombination signal sequences along the TCRalpha locus. Here we show that chromatin acetylation along the first Jalpha segments is under the dependence of the T early alpha element (TEA), located upstream of TCRJalpha locus. The targeted deletion of TEA leads to an absence of histones H3 and H4 tail acetylation, while maintaining histone acetylation in the region spanning downstream Jalpha segments. During thymocyte maturation, TEA-dependent histone acetylation appears at immature single-positive stage, known to represent the stage of ValphaJalpha initiation. TEA-dependent histone acetylation of the most upstream Jalpha segments leads to enhanced DNA accessibility thus optimizing TCRJalpha usage and increasing Ag receptor diversity potential.
Mauvieux
Laurent
L
Développement normal et pathologique du système immunitaire, INSERM U429, Hôpital Necker-Enfants-Malades, Paris, France.
Villey
Isabelle
I
de Villartay
Jean-Pierre
JP
D000107:Acetylation; D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D002843:Chromatin; D006657:Histones; D008565:Membrane Proteins; C087435:Slc7a2 protein, mouse