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Molecular and Cellular Biology, July 2007, p. 5184-5200, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.02091-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Histone Deacetylase 7 Functions as a Key Regulator of Genes Involved in both Positive and Negative Selection of Thymocytes{triangledown}

Herbert G. Kasler and Eric Verdin*

Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, California 94158

Received 8 November 2006/ Returned for modification 19 December 2006/ Accepted 23 April 2007

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 expressed HDAC7 mutant proteins in a T-cell line and use DNA microarrays to identify transcriptional targets of HDAC7 in T cells. The changes in gene expression levels were 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 thymic selection, primarily via modulating the coupling between antigen receptor engagement and downstream signaling events. Consistent with the model that HDAC7 may play an important role in both positive and negative thymic selection, the expression of distinct HDAC7 mutants or the abrogation of HDAC7 expression can either enhance or inhibit the signal-dependent differentiation of a CD4+/CD8+ cell line.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, CA 94158. Phone: (415) 734-4808. Fax: (415) 355-0855. E-mail: everdin{at}gladstone.ucsf.edu

{triangledown} Published ahead of print on 30 April 2007.

Molecular and Cellular Biology, July 2007, p. 5184-5200, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.02091-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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