Gene Regulation by HDAC7 in Thymic Selection

Histone deacetylase 7 (HDAC7) is highly expressed in CD4+/CD8+ thymocytes and functions as a signal-dependent repressor of gene transcription during T cell development. In this study, we express HDAC7 mutant proteins in a T cell line and use DNA microarrays to identify transcriptional targets of HDAC7 in T cells. Gene expression changes are compared to differential gene expression profiles associated with positive and negative thymic selection. This analysis reveals that HDAC7 regulates an extensive set of genes that are differentially expressed during both positive and negative thymic selection. Many of these genes play important functional roles in positive and negative selection, primarily via coupling between antigen receptor and downstream signaling events. Keywords: microarray gene expression profiling, comparison of perturbation of HDAC7 gene function with differential expression during thymic selection DO11.10 cells were transduced with different viruses encoding mutants of HDAC7, MEF2D, or Nur77. All microarrays were hybridized with untreated DO11.10 cells in one channel and transdced/treated cells in the other. Hybridizations are done with 4-12 replicates. DO11.10 TCR-transgenic thymocytes were also compared to MHC-deficient thymocytes and DO11.10 TCR-transgenic thymocytes from animals that had been injected with antigenic peptide at different timepoints prior to harvest of thymocytes.