B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites
B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites
复制标题
DOI：
10.4049/jimmunol.173.9.5556
复制
发表时间：
2004-11-01
影响因子：
4.4
通讯作者：
Calame, KL
中科院分区：
文献类型：
--
作者：
Kuo, TC;Calame, KL
转录抑制因子 B 淋巴细胞诱导成熟蛋白 1 (Blimp-1) 在一些分化细胞中表达，是 B 细胞终末分化所必需的。为了便于鉴定Blimp-1靶基因，我们确定了Blimp-1的最佳DNA识别序列。该共识与 IFN 调节因子 (IRF) 识别的包含序列 GAAAG 的位点子集非常相似。通过结合竞争和平衡解离常数的测定，我们表明Blimp-1、IRF-1和IRF-2对包含该序列的功能重要的调控位点具有相似的结合亲和力。然而，Blimp-1 并不结合所有 IRF 位点，并且具体不识别缺少 GAAAG 序列的 IRF-4/PU.1 或 IRF-8 位点。染色质免疫沉淀研究表明，正如体外结合参数所预测的那样，Blimp-1、IRF-1 和 IRF-2 在体内均结合 IFN-β 启动子，并且在共转染中，Blimp-1 抑制 IRF-1 依赖性的 IFN-β 启动子激活。因此，我们的数据表明，Blimp-1 在体内与 IRF 蛋白的子集竞争，并有助于预测可能受影响的位点和 IRF 家族成员。
The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is expressed in some differentiated cells and is required for terminal differentiation of B cells. To facilitate identification of Blimp-1 target genes, we have determined the optimal DNA recognition sequence for Blimp-1. The consensus is very similar to a subset of sites recognized by IFN regulatory factors (IRFs) that contain the sequence GAAAG. By binding competition and determination of equilibrium dissociation constants, we show that Blimp-1, IRF-1, and IRF-2 have similar binding affinities for functionally important regulatory sites containing this sequence. However, Blimp-1 does not bind to all IRF sites, and specifically does not recognize IRF-4/PU.1 or IRF-8 sites lacking the GAAAG sequence. Chromatin immunoprecipitation studies showed that Blimp-1, IRF-1, and IRF-2 all bind the IFN-beta promoter in vivo, as predicted by the in vitro binding parameters, and in cotransfections Blimp-1 inhibits IRF-1-dependent activation of the IFN-beta promoter. Thus, our data suggest that Blimp-1 competes in vivo with a subset of IRF proteins and help predict the sites and IRF family members that may be affected.