Abstract
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 TCRß-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 αß 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.
Original language | English (US) |
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Pages (from-to) | 3854-3865 |
Number of pages | 12 |
Journal | Molecular and cellular biology |
Volume | 35 |
Issue number | 22 |
DOIs | |
State | Published - 2015 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology