Majumder Parimal, Gomez Jorge A, Boss Jeremy M
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Biol Chem. 2006 Jul 7;281(27):18435-43. doi: 10.1074/jbc.M601298200. Epub 2006 May 4.
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 approximately 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.
人类主要组织相容性复合体II类（MHC-II）区域编码一组多态性异二聚体糖蛋白HLA-DR、-DQ和-DP，它们在抗原呈递中发挥作用。HLA-DRB1和HLA-DQA1被约44 kb的DNA隔开，它们编码的MHC-II蛋白在不同的MHC-II异二聚体中发挥作用，且转录方向相反。在HLA-DRB1和HLA-DQA1之间的基因间序列中发现了一个高乙酰化区域，称为XL9。通过染色质免疫沉淀和体外DNA结合研究确定，乙酰化峰值与结合绝缘子蛋白CCCTC结合因子的序列一致。还发现XL9与核基质相关。对XL9区域的活性进行了检测，发现它是一种有效的增强子阻断元件。这些结果表明，XL9区域可能已经进化以分隔HLA-DR和HLA-DQ基因的转录单元。
