Histone deacetylase 3 is required for efficient T cell development

Kristy R. Stengel, Yue Zhao, Nicholas J. Klus, Jonathan F. Kaiser, Laura E. Gordy, Sebastian Joyce, Scott W. Hiebert, Alyssa R. Summers

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 languageEnglish (US)
Pages (from-to)3854-3865
Number of pages12
JournalMolecular and cellular biology
Volume35
Issue number22
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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