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J. Biol. Chem., Vol. 281, Issue 27, 18435-18443, July 7, 2006

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The Human Major Histocompatibility Complex Class II HLA-DRB1 and HLA-DQA1 Genes Are Separated by a CTCF-binding Enhancer-blocking Element^*

From the Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

The human major histocompatibility complex class II (MHC-II) region encodes a cluster of polymorphic heterodimeric glycoproteins HLA-DR, -DQ, and -DP that functions in antigen presentation. Separated by 44 kb of DNA, the HLA-DRB1 and HLA-DQA1 encode MHC-II proteins that function in separate MHC-II heterodimers and are diametrically transcribed. A region of high acetylation located in the intergenic sequences between HLA-DRB1 and HLA-DQA1 was discovered and termed XL9. The peak of acetylation coincided with sequences that bound the insulator protein CCCTC-binding factor as determined by chromatin immunoprecipitations and in vitro DNA binding studies. XL9 was also found to be associated with the nuclear matrix. The activity of the XL9 region was examined and found to be a potent enhancer-blocking element. These results suggest that the XL9 region may have evolved to separate the transcriptional units of the HLA-DR and HLA-DQ genes.

Received for publication, February 9, 2006 , and in revised form, April 25, 2006.

^* This work was supported by National Institutes of Health Grants GM47310 and AI34000 (to J. M. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Emory University, 1510 Clifton Rd., Atlanta, GA 30322. Tel.: 404-727-5973; Fax: 404-727-1719; E-mail: boss{at}microbio.emory.edu.

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