Function and Evolution of C2H2 Zinc Finger Arrays

Function and Evolution of C2H2 Zinc Finger Arrays
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DOI:
10.1007/978-90-481-9069-0_4
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发表时间:
2011-01-01
期刊:
HANDBOOK OF TRANSCRIPTION FACTORS
影响因子:
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通讯作者:
Caetano-Anolles, Derek
Caetano-Anolles, Derek
中科院分区:
其他
文献类型:
--
作者:
Stubbs, Lisa;Sun, Younguk;Caetano-Anolles, Derek

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Kruppel-type或C2H2锌指是真核转录因子(Tf)蛋白中主要的DNA结合基序。在Kruppel-type(KZNF)转录因子中,KZNF基序排列在3到40个串联单元的阵列中,这些串联单元共同定义蛋白质独特的DNA识别特性。每个手指包含位于特定位置的四个氨基酸,当KZNF阵列绕着阿尔法螺旋的主要凹槽缠绕时,这些氨基酸与DNA序列中的相邻核苷酸直接接触。这种排列在KZNF阵列的氨基酸序列和靶结合位点的核苷酸序列之间创建了一种密切的和潜在的可预测的关系。在脊椎动物中,模块KZNF基序的大量可能组合和排列,以及KZNF阵列长度的增加,创造了大量功能独特的转铁蛋白。在进化过程中,这种多功能的DNA结合基序的特性已经被独立地开发了许多次,通过附着于赋予蛋白质激活、抑制或其他活动的效应器基序。一旦被创造出来,这些新颖的发明中的一些已经在特定的进化分支中扩展,创造了血统或物种独特的大家族。本章综述了真核生物KZNFTf蛋白的性质及其显著的进化历史,尤其是在不同后生动物物种中主导Tf景观的大家族。
Kruppel-type or C2H2 zinc fingers represent a dominant DNA-binding motif in eukaryotic transcription factor (TF) proteins. In Kruppel-type (KZNF) TFs, KZNF motifs are arranged in arrays of three to as many as 40 tandem units, which cooperate to define the unique DNA recognition properties of the protein. Each finger contains four amino acids located at specific positions, which are brought into direct contact with adjacent nucleotides in the DNA sequence as the KZNF array winds around the major groove of the alpha helix. This arrangement creates an intimate and potentially predictable relationship between the amino acid sequence of KZNF arrays and the nucleotide sequence of target binding sites. The large number of possible combinations and arrangements of modular KZNF motifs, and the increasing lengths of KZNF arrays in vertebrate species, has created huge repertoires of functionally unique TF proteins. The properties of this versatile DNA-binding motif have been exploited independently many times over the course of evolution, through attachment to effector motifs that confer activating, repressing or other activities to the proteins. Once created, some of these novel inventions have expanded in specific evolutionary clades, creating large families of TFs that are lineage- or species-unique. This chapter reviews the properties and their remarkable evolutionary history of eukaryotic KZNF TF proteins, with special focus on large families that dominate the TF landscapes in different metazoan species.