Moreno C S, Beresford G W, Louis-Plence P, Morris A C, Boss J M
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Immunity. 1999 Feb;10(2):143-51. doi: 10.1016/s1074-7613(00)80015-1.
The X2 box of MHC class II promoters is homologous to TRE/CRE elements and is required for expression of MHC class II genes. The X2 box-specific DNA binding activity, X2BP, was purified to homogeneity, sequenced, and identified as CREB. Transient transactivation experiments showed that CREB can cooperate with CIITA to enhance activation of transcription from MHC class II promoters in a dose-dependent manner. Binding of CREB to the class II promoter in vivo was demonstrated by a chromatin immunoprecipitation assay. Additionally, ICER, a dominant inhibitor of CREB function, was found to repress class II expression. These results demonstrate that CREB binds to the X2 box in vivo and cooperates with CIITA to direct MHC class II expression.
MHC II类启动子的X2框与TRE/CRE元件同源,是MHC II类基因表达所必需的。X2框特异性DNA结合活性X2BP被纯化至同质,测序并鉴定为CREB。瞬时反式激活实验表明,CREB可与CIITA协同,以剂量依赖方式增强MHC II类启动子的转录激活。染色质免疫沉淀实验证明了CREB在体内与II类启动子的结合。此外,发现CREB功能的显性抑制剂ICER可抑制II类表达。这些结果表明,CREB在体内与X2框结合,并与CIITA协同指导MHC II类表达。