Negative transcriptional regulation mediated by thyroid hormone response element 144 requires binding of the multivalent factor CTCF to a novel target DNA sequence
Negative transcriptional regulation mediated by thyroid hormone response element 144 requires binding of the multivalent factor CTCF to a novel target DNA sequence
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DOI：
10.1074/jbc.274.38.27092
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发表时间：
1999-09-17
影响因子：
4.8
通讯作者：
Filippova, GN
中科院分区：
文献类型：
--
作者：
Awad, TA;Bigler, J;Filippova, GN
“多价”11 锌指 CCTC 结合因子 (CTCF) 的 DNA 靶位点异常长（类似于 50 个碱基对）且显着不同。与甲状腺受体 (TR) 结合，CTCF 与溶菌酶基因转录沉默子结合，介导甲状腺激素反应元件 (TRE) 依赖性转录抑制。我们测试了其他 TRE（除了存在 TR 结合位点之外还需要邻近序列来实现转录功能）是否还可能包含以前未识别的 CTCF 结合位点。其中一个候选 DNA 区域是包含 TRE 的基因组元件，该候选 DNA 区域先前由 Bigler 和 Eisenman 分离（Bigler, J., and Eisenman, R. N. (1995) EMBO J, 14, 5710-5723）。 144. 我们已经鉴定出一个新的 CTCF 靶序列，该序列与 144 片段内的 TR 结合位点相邻。溶菌酶沉默子中的 CTCF 识别核苷酸与 144 个序列中的 CTCF 识别核苷酸的比较揭示了相似性和差异。几个 C 末端 CTCF 锌指对结合每个序列的贡献不同。消除 CTCF 结合的突变会损害 144 介导的负转录调节。因此，144 元件提供了功能上重要的复合“TRE 加 CTCF 结合位点”调节元件的另一个例子，表明 CTCF 与核受体的类固醇/甲状腺超家族合作介导 TRE 依赖性转录抑制的重要作用。
DNA target sites for a "multivalent" 11-zinc-finger CCTC-binding factor (CTCF) are unusually long (similar to 50 base pairs) and remarkably different, In conjunction with the thyroid receptor (TR), CTCF binding to the lysozyme gene transcriptional silencer mediates the thyroid hormone response element (TRE)-dependent transcriptional repression. We tested whether other TREs, which in addition to the presence of a TR binding site require neighboring sequences for transcriptional function, might also contain a previously unrecognized binding site(s) for CTCF, One such candidate DNA region, previously isolated by Bigler and Eisenman (Bigler, J., and Eisenman, R. N. (1995) EMBO J, 14, 5710-5723), is the TRE-containing genomic element 144. We have identified a new CTCF target sequence that is adjacent to the TR binding site within the 144 fragment. Comparison of CTCF recognition nucleotides in the lysozyme silencer and in the 144 sequences revealed both similarities and differences. Several C-terminal CTCF zinc fingers contribute differently to binding each of these sequences. Mutations that eliminate CTCF binding impair 144-mediated negative transcriptional regulation, Thus, the 144 element provides an additional example of a functionally significant composite "TRE plus CTCF binding site" regulatory element suggesting an important role for CTCF in cooperation with the steroid/thyroid superfamily of nuclear receptors to mediate TRE-dependent transcriptional repression.