G10BP, an E1A-inducible negative regulator of Sp1, represses transcription of the rat fibronectin gene
G10BP, an E1A-inducible negative regulator of Sp1, represses transcription of the rat fibronectin gene
复制标题
G10BP 是一种 E1A 诱导的 Sp1 负调节因子，抑制大鼠纤连蛋白基因的转录
DOI：
--
复制
发表时间：
1995
影响因子：
5.3
通讯作者：
K. Oda
中科院分区：
文献类型：
--
作者：
Mitsuhiro Suzuki;Chizuko Kuroda;Eri Oda;S. Tsunoda;Takeshi Nakamura;T. Nakajima;K. Oda
由腺病毒E1A和E1B基因转化的大鼠3Y1衍生细胞系XhoC中纤维连接蛋白（FN）基因的下调似乎是由诱导负调节因子G10BP引起的，G10BP与启动子中的三个富含g的序列结合（T. Nakamura， T. Nakajima， S. Tsunoda， S. Nakada， K. Oda， H. Tsurui, and a . Wada， J. Virol. 66:6436-6450, 1992）。这些是G10拉伸和两个GC盒，由G10拉伸和一个内部C残基插入组成。G10BP和Sp1 （ggggcgg）的识别序列在这些GC盒中重叠。为了分析G10BP下调的机制，采用DNA亲和层析纯化G10BP，估计其分子量约为30 kDa。通过在这些富含g的序列中用ATCC或CTTA取代GGGG序列来修饰启动子，使Sp1基序保持完整，并用T延伸取代Sp1基序。在体内和体外，FN启动子-氯霉素乙酰转移酶融合基因携带一个或多个这些富g序列的碱基替换的转录表明，尽管下游GC盒（GCd）起主要作用，但任何富g序列的碱基替换都会导致启动子活性降低。G10BP的加入严重抑制了体外携带野生型GCd的FN启动子的活性，而携带突变型GCd的启动子不受影响。凝胶位移法分析了G10BP和Sp1对各富g序列的结合亲和力，结果表明G10BP与GCd的结合较强，与G10拉伸的结合中等，与GCu的结合较弱，而Sp1与GCu的结合较强，与GCd的结合中等，与G10拉伸的结合较弱。G10BP抑制Sp1与GCd的结合和G10的拉伸，而与GCu的结合不受影响。这些结果表明，在XhoC细胞中，抑制FN基因转录主要是通过G10BP排除Sp1与GCd的结合，G10BP是一类新的Sp1负调控因子。
Downregulation of the fibronectin (FN) gene in a rat 3Y1 derivative cell line, XhoC, transformed by the adenovirus E1A and E1B genes seems to be caused by the induction of a negative regulator, G10BP, which binds to three G-rich sequences in the promoter (T. Nakamura, T. Nakajima, S. Tsunoda, S. Nakada, K. Oda, H. Tsurui, and A. Wada, J. Virol. 66:6436-6450, 1992). These are the G10 stretch and two GC boxes consisting of the G10 stretch with one internal C residue insertion. The recognition sequences of G10BP and Sp1 (GGGCGG) overlap in these GC boxes. To analyze the mechanism of the downregulation, G10BP was purified by DNA affinity chromatography, and its molecular mass was estimated to be about 30 kDa. The promoter was modified by substituting the sequence GGGG with ATCC or CTTA in these G-rich sequences, leaving the Sp1 motif intact, and by replacing the Sp1 motif by the T stretch. Transcription of FN promoter-chloramphenicol acetyltransferase fusion genes carrying the base substitution in one or more of these G-rich sequences both in vivo and in vitro revealed that the base substitution in any G-rich sequence results in reduction of promoter activity, although the downstream GC box (GCd) plays a primary role. The addition of G10BP severely inhibited the activities of the FN promoters carrying the wild-type GCd in vitro, while the promoters carrying the mutant GCd were unaffected. The binding affinity of G10BP and Sp1 to each of the G-rich sequences, analyzed by gel shift assays, indicated that G10BP binds strongly to the GCd, moderately to the G10 stretch, and weakly to GCu, while Sp1 binds strongly to GCu, moderately to GCd, and weakly to the G10 stretch. Sp1 binding to GCd and the G10 stretch was inhibited by G10BP, while binding to GCu was unaffected. These results indicate that FN gene transcription is inhibited in XhoC cells primarily by exclusion of Sp1 binding to GCd by G10BP and that G10BP is a new class of Sp1 negative regulator.
纤连蛋白基因的组织为进化过程中的外显子改组提供了证据。
DOI：
10.1002/j.1460-2075.1987.tb02545.x
发表时间：
1987
期刊：
The EMBO journal
影响因子：
--
作者：
Patel,RS;Odermatt,E;Schwarzbauer,JE;Hynes,RO
通讯作者：
Hynes,RO
影响因子：
56.9
作者：
BRIGGS, MR;KADONAGA, JT;TJIAN, R
通讯作者：
TJIAN, R