| First Author | Nozaki M | Year | 2011 |
| Journal | Int Immunol | Volume | 23 |
| Issue | 5 | Pages | 297-305 |
| PubMed ID | 21421735 | Mgi Jnum | J:172075 |
| Mgi Id | MGI:5003396 | Doi | 10.1093/intimm/dxr005 |
| Citation | Nozaki M, et al. (2011) Regulation of TCR V{gamma}2 gene rearrangement by the helix-loop-helix protein, E2A. Int Immunol 23(5):297-305 |
| abstractText | 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 TCRgamma locus, rearrangement of the Vgamma2 gene predominates over Vgamma3 rearrangement in the adult thymus. This preferential rearrangement is likely due to the differential accessibility of the individual Vgamma genes, because the levels of germ line transcription and histone acetylation of the Vgamma genes are well correlated with the rearrangement frequency in adult thymocytes. However, factors responsible for the differential regulation of the Vgamma gene rearrangement have been largely unknown. In this study, we demonstrated that Vgamma2 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 Vgamma2 chromatin, since germ line transcription and histone acetylation of the Vgamma2 gene were reduced in an E2A dosage-dependent manner. We further showed that E2A bound around the Vgamma2 gene in vivo and we identified two canonical E-box sites downstream of Vgamma2, 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 Vgamma2 chromatin, thereby facilitating Vgamma2 rearrangement in the adult thymus. |
