Transcription of the human cell cycle regulated BUB1B gene requires hStaf/ZNF143.
Transcription of the human cell cycle regulated BUB1B gene requires hStaf/ZNF143.
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DOI：
10.1093/nar/gkm239
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发表时间：
2007
影响因子：
14.9
通讯作者：
Carbon P
中科院分区：
文献类型：
--
作者：
Myslinski E;Gérard MA;Krol A;Carbon P
BubR1是介导纺锤体检查点激活的关键蛋白。失去这种检查点控制会导致染色体不稳定和非整倍体。本文研究了编码BubR1的细胞周期调控的人BUB1B基因的转录调控。在翻译起始密码子上游含有464 碱基的最小BUB1B基因启动子足以满足细胞周期调控启动子的活性。通过凝胶滞留实验、突变型BUB1B启动子-报告基因的瞬时表达和染色质免疫沉淀实验，证实了转录因子hStaf/ZNF143在BUB1B基因表达中的关键作用。鉴定了两个系统发育保守的hStaf/ZNF143结合位点(SBS)，它们是BUB1B启动子活性所必需的。此外，我们还发现，覆盖转录起始点的区域包含与启动子(INR)、细胞周期依赖(CDE)和细胞周期基因同源区域(CHR)元件同源的保守盒。CDE和CHR元件的突变导致BUB1B转录的细胞周期调节减弱。这些结果表明，BUB1B基因转录受普遍表达的hStaf/ZNF143正调控，CDE-CHR串联元件是BUB1B基因G2/M特异性转录所必需的。
BubR1 is a key protein mediating spindle checkpoint activation. Loss of this checkpoint control results in chromosomal instability and aneuploidy. The transcriptional regulation of the cell cycle regulated human BUB1B gene, which encodes BubR1, was investigated in this report. A minimal BUB1B gene promoter containing 464 bp upstream from the translation initiation codon was sufficient for cell cycle regulated promoter activity. A pivotal role for transcription factor hStaf/ZNF143 in the expression of the BUB1B gene was demonstrated through gel retardation assays, transient expression of mutant BUB1B promoter–reporter gene constructs and chromatin immunoprecipitation assay. Two phylogenetically conserved hStaf/ZNF143-binding sites (SBS) were identified which are indispensable for BUB1B promoter activity. In addition, we found that the domain covering the transcription start sites contains conserved boxes homologous to initiator (Inr), cell cycle dependent (CDE) and cell cycle genes homology regions (CHR) elements. Mutations within the CDE and CHR elements led to diminished cell cycle regulation of BUB1B transcription. These results demonstrate that BUB1B gene transcription is positively regulated by hStaf/ZNF143, a ubiquitously expressed factor, and that the CDE-CHR tandem element was essential for G2/M-specific transcription of the BUB1B gene.
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影响因子：
4.8
作者：
Grossman, CE;Qian, YM;Perl, A
通讯作者：
Perl, A
影响因子：
4.4
作者：
Barski, OA;Papusha, VZ;Gabbay, KH
通讯作者：
Gabbay, KH
影响因子：
4.4
作者：
Davenport, JW;Fernandes, ER;Goorha, R
通讯作者：
Goorha, R
影响因子：
4.8
作者：
Kubota, H;Yokota, S;Yura, T
通讯作者：
Yura, T
影响因子：
4.4
作者：
RAGOUSSIS, J;SENGER, G;TROWSDALE, J
通讯作者：
TROWSDALE, J