COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein
COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein
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DOI：
10.1042/bj20020496
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发表时间：
2002-12-01
影响因子：
4.1
通讯作者：
Leid, M
中科院分区：
文献类型：
--
作者：
Avram, D;Fields, A;Leid, M
鸡卵清蛋白上游启动子转录因子（COUP-TF）相互作用蛋白1和2 [CTIP 1/Evi 9/B细胞白血病（Bcl）I1 a和CTIP 2/Bcl 11 B b]是高度相关的C、H、锌指蛋白，其在脑和免疫系统中大量表达，并且与免疫系统恶性肿瘤相关。采用选择程序分离CTIP 1的高亲和力DNA结合位点。在这些研究中鉴定的DNA上的核心结合位点5 '-GGCCGG-3'（上链）与典型GC盒高度相关，并且在体外被CTIP 1寡聚复合物结合。此外，CTIP 1和CTIP 2抑制了携带多聚化CTIP结合位点的报告基因的转录，并且这种抑制既不被抑制素A（已知I类和II类组蛋白脱乙酰酶的抑制剂）逆转，也不被COUP-TF家族成员的共转染刺激。这些结果表明，CTIP 1是一个序列特异性的DNA结合蛋白和真正的转录抑制因子，能够独立于COUP-TF家族成员发挥作用。这些发现可能与CTIP在不表达COUP-TF家族成员的细胞（例如造血和免疫系统的细胞）中的生理和/或病理作用有关。
Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting proteins 1 and 2 [CTIP1/Evi9/B cell leukaemia (Bcl) I1a and CTIP2/Bcl11b respectively] are highly related C,H, zinc finger proteins that are abundantly expressed in brain and the immune system, and are associated with immune system malignancies. A selection procedure was employed to isolate high-affinity DNA binding sites for CTIP1. The core binding site on DNA identified in these studies, 5'-GGCCGG-3' (upper strand), is highly related to the canonical GC box and was bound by a CTIP1 oligomeric complex(es) in vitro. Furthermore, both CTIP1 and CTIP2 repressed transcription of a reporter gene harbouring a multimerized CTIP binding site, and this repression was neither reversed by trichostatin A (an inhibitor of known class I and II histone deacetylases) nor stimulated by cotransfection of a COUP-TF family member. These results demonstrate that CTIP1 is a sequence-specific DNA binding protein and a bona fide transcriptional repressor that is capable of functioning independently of COUP-TF family members. These findings may be relevant to the physiological and/or pathological action(s) of CTIPs in cells that do not express COUP-TF family members, such as cells of the haematopoietic and immune systems.