Histone Deacetylase 3 Is Required for Efficient T Cell Development.

Stengel KR, Zhao Y, Klus NJ, Kaiser JF, Gordy LE, Joyce S, Hiebert SW, Summers AR
Mol Cell Biol. 2015 35 (22): 3854-65

PMID: 26324326 · PMCID: PMC4609739 · DOI:10.1128/MCB.00706-15

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 TCRβ-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 αβ 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.

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MeSH Terms (18)

Animals bcl-X Protein CD4 Antigens CD4-Positive T-Lymphocytes CD8 Antigens CD8-Positive T-Lymphocytes Cell Differentiation Gene Deletion Gene Expression Regulation, Developmental Histone Deacetylases Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins c-bcl-2 Receptors, Antigen, T-Cell, alpha-beta T-Lymphocytes

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