Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation
Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation
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DOI：
10.1016/j.jmb.2006.04.016
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发表时间：
2006-06-16
影响因子：
5.6
通讯作者：
Nishikawa, Ken
中科院分区：
文献类型：
--
作者：
Minezaki, Yoshiaki;Homma, Keiichi;Nishikawa, Ken
人类转录调控因子，如激活子、阻遏子和增强子结合因子，在两个方面与原核生物有很大不同：人类的平均序列比原核生物长两倍多，而与已知结构域比对的序列比例在人类转录因子(TF)中为31%，不到细菌TF的一半(72%)。通过无序预测程序识别出本质无序（ID）区域，并发现其与现有的实验数据非常一致。通过 Swiss-Prot 数据库的实验证据对 401 个人类 TF 进行分析表明，高达 49% 的人类 TF 整个序列被 ID 区域占据。超过一半的人类 TF 由小的 DNA 结合域 (DBD) 和长 ID 区域组成，这些区域经常夹在未分配的区域之间。除了 DBD 和 ID 区域之外，其余 TF 还具有结构域。实验研究，特别是 NMR 的实验研究表明，未结合 TF 中的反式激活结构域通常是非结构化的，但在与其伴侣结合后会变得结构化。尽管 ID 区域的发生率很高，但人类和小鼠 TF 直系同源物的序列仍具有 90.5% 的一致性，这可能反映了 ID 区域发挥的重要功能作用。一般来说，ID 区域在真核生物的 TF 中占据很高的比例，但在原核生物中则不然。我们讨论了这种二分法的含义及其在转录调控和进化中的功能作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
Human transcriptional regulation factors, such as activators, repressors, and enhancer-binding factors are quite different from their prokaryotic counterparts in two respects: the average sequence in human is more than twice as long as that in prokaryotes, while the fraction of sequence aligned to domains of known structure is 31% in human transcription factors (TFs), less than half of that in bacterial TFs (72%). Intrinsically disordered (ID) regions were identified by a disorder-prediction program, and were found to be in good agreement with available experimental data. Analysis of 401 human TFs with experimental evidence from the Swiss-Prot database showed that as high as 49% of the entire sequence of human TFs is occupied by ID regions. More than half of the human TFs consist of a small DNA binding domain (DBD) and long ID regions frequently sandwiching unassigned regions. The remaining TFs have structural domains in addition to DBDs and ID regions. Experimental studies, particularly those with NMR, revealed that the transactivation domains in unbound TFs are usually unstructured, but become structured upon binding to their partners. The sequences of human and mouse TF orthologues are 90.5% identical despite a high incidence of ID regions, probably reflecting important functional roles played by ID regions. In general ID regions occupy a high fraction in TFs of eukaryotes, but not in prokaryotes.. Implications of this dichotomy are discussed in connection with their functional roles in transcriptional regulation and evolution. (c) 2006 Elsevier Ltd. All rights reserved.