A novel SATB1 binding site in the BCL2 promoter region possesses transcriptional regulatory function.
A novel SATB1 binding site in the BCL2 promoter region possesses transcriptional regulatory function.
复制标题
BCL2启动子区的一个新的SATB1结合位点具有转录调节功能
DOI：
10.1016/s1674-8301(10)60060-7
复制
发表时间：
2010-11
影响因子：
2.3
通讯作者：
Sun, Yujie
中科院分区：
文献类型：
--
作者：
Gong, Feiran;Sun, Luan;Sun, Yujie
BCL 2是细胞凋亡的关键调节因子。我们的前期工作已经证明，特殊的富含AT的序列结合蛋白1（SATB 1）与BCL 2的表达呈正相关。在本研究中，我们报告了一个新的SATB 1结合位点位于BCL 2基因的P1和P2启动子之间。通过凝胶迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）在体外和体内研究了通过生物信息学分析预测的候选SATB 1结合序列。其中一段25 bp的序列命名为SB1，经鉴定为SATB 1结合位点。利用Jurkat细胞双荧光素酶报告基因系统进一步检测SB1的调控功能及其与SATB 1的相关性。我们发现SB1可以负调控报告基因的活性。SATB 1结合位点的突变进一步抑制了该活性。SATB 1的敲除也增强了SB 1的这种负面影响。我们的数据表明，SB 1序列具有负转录调控功能，这种功能可以被SATB 1拮抗。
BCL2 is a key regulator of apoptosis. Our previous work has demonstrated that special AT-rich sequence-binding protein 1 (SATB1) is positively correlated with BCL2 expression. In the present study, we report a new SATB1 binding site located between P1 and P2 promoters of the BCL2 gene. The candidate SATB1 binding sequence predicted by bioinformatic analysis was investigated in vitro and in vivo by electrophoretic gel mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP). One 25-bp sequence, named SB1, was confirmed to be SATB1 binding site. The regulatory function of SB1 and its relevance to SATB1 were further examed with dual-luciferase reporter assay system in Jurkat cells. We found that SB1 could negatively regulate reporter gene activity. Mutation of SATB1 binding site further repressed the activity. Knockdown of SATB1 also enhanced this negative effect of SB1. Our data indicate that the SB1 sequence possesses negative transcriptional regulatory function and this function can be antagonized by SATB1.