First Author | Stengel KR | Year | 2015 |
Journal | Mol Cell Biol | Volume | 35 |
Issue | 22 | Pages | 3854-65 |
PubMed ID | 26324326 | Mgi Jnum | J:235845 |
Mgi Id | MGI:5803781 | Doi | 10.1128/MCB.00706-15 |
Citation | Stengel KR, et al. (2015) Histone Deacetylase 3 Is Required for Efficient T Cell Development. Mol Cell Biol 35(22):3854-65 |
abstractText | Hdac3 is a key target for Hdac inhibitors that are efficacious in cutaneous T cell lymphoma. Moreover, the regulation of chromatin structure is critical as thymocytes transition from an immature cell with open chromatin to a mature T cell with tightly condensed chromatin. To define the phenotypes controlled by Hdac3 during T cell development, we conditionally deleted Hdac3 using the Lck-Cre transgene. This strategy inactivated Hdac3 in the double-negative stages of thymocyte development and caused a significant impairment at the CD8 immature single-positive (ISP) stage and the CD4/CD8 double-positive stage, with few mature CD4(+) or CD8(+) single-positive cells being produced. When Hdac3(-/-) mice were crossed with Bcl-xL-, Bcl2-, or TCRbeta-expressing transgenic mice, a modest level of complementation was found. However, when the null mice were crossed with mice expressing a fully rearranged T cell receptor alphabeta transgene, normal levels of CD4 single-positive cells were produced. Thus, Hdac3 is required for the efficient transit from double-negative stage 4 through positive selection. |