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Article
Nature Immunology  4, 1074 - 1082 (2003)
Published online: 5 October 2003; | doi:10.1038/ni985

Enhancement of CIITA transcriptional function by ubiquitin

Susanna F Greer1, 4, Eleni Zika2, Brian Conti3, Xin-Sheng Zhu1, 5 & Jenny P-Y Ting1, 4

1  Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

2  Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

3  Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

4  Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

5  Present address: Department of Periodontics and Endodontics, School of Dental Medicine, The State University of New York at Buffalo, Buffalo, New York 14214, USA.

Correspondence should be addressed to Jenny P-Y Ting panyun@med.unc.edu
Although increasing evidence indicates that there is a direct link between ubiquitination and mono-ubiquitination and transcription in yeast, this link has not been demonstrated in higher eukaryotes. Here we show that the major histocompatibility complex (MHC) class II transactivator (CIITA), which is required for expression of genes encoding MHC class II molecules, is ubiquitinated. This ubiquitination enhanced the association of CIITA with both MHC class II transcription factors and the MHC class II promoter, resulting in an increase in transactivation function and in the expression of MHC class II mRNA. The degree of CIITA ubiquitination was controlled by histone acetylases (HATs) and deacetylases (HDACs), indicating that the crucial cellular processes mediated by these enzymes are linked to regulate transcription. Thus, ubiquitin positively regulates a mammalian coactivator by enhancing its assembly at the promoter.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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