title: Regulation of TCR Vγ2 gene rearrangement by the helix-loop-helix protein, E2A.
abstract: V(D)J recombination of Ig and TCR genes is strictly regulated by the accessibility of target gene chromatin in a lineage- and stage-specific manner. In the mouse TCRγ locus, rearrangement of the Vγ2 gene predominates over Vγ3 rearrangement in the adult thymus. This preferential rearrangement is likely due to the differential accessibility of the individual Vγ genes, because the levels of germ line transcription and histone acetylation of the Vγ genes are well correlated with the rearrangement frequency in adult thymocytes. However, factors responsible for the differential regulation of the Vγ gene rearrangement have been largely unknown. In this study, we demonstrated that Vγ2 rearrangement in the adult thymus was substantially reduced in mice deficient for the basic helix-loop-helix protein, E2A. The decreased rearrangement is likely caused by the reduced accessibility of Vγ2 chromatin, since germ line transcription and histone acetylation of the Vγ2 gene were reduced in an E2A dosage-dependent manner. We further showed that E2A bound around the Vγ2 gene in vivo and we identified two canonical E-box sites downstream of Vγ2, to which E2A can bind in vitro. Furthermore, these two E-box sites had the ability to activate transcription upon E2A over-expression. These data suggest that E2A directly binds to and increases accessibility of Vγ2 chromatin, thereby facilitating Vγ2 rearrangement in the adult thymus.
authors.affiliation: Department of Developmental Medicine, Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka 594-1101, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nozaki
authors.forename: Kousho
authors.initials: K
authors.lastname: Wakae
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tamaki
authors.forename: Shuji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Kiyouhisa
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Uejima
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.forename: Itaru
authors.initials: I
authors.lastname: Yanagihara
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C075668:Tcf3 protein, mouse