Conserved interaction between distinct Kruppel-associated box domains and the transcriptional intermediary factor 1 β
Conserved interaction between distinct Kruppel-associated box domains and the transcriptional intermediary factor 1 β
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DOI：
10.1073/pnas.041616998
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发表时间：
2001-02-13
影响因子：
11.1
通讯作者：
Losson, R
中科院分区：
文献类型：
--
作者：
Abrink, M;Ortiz, JA;Losson, R
Kruppel-associated box （KRAB）结构域，最初被鉴定为存在于许多kruppel型锌指蛋白中的75-aa序列，是一种有效的dna结合依赖性转录抑制结构域，被认为通过与转录中介因子1 (TIF1) β相互作用发挥作用。在序列比较和系统发育分析的基础上，我们最近定义了三个不同的KRAB结构域亚家族。在本研究中，对每个亚家族的个体成员进行了转录抑制和与TIF1 β和其他两个密切相关的家族成员（TIF1 α和TIF1 γ）的相互作用测试。所有的KRAB变异体都显示：(i)在哺乳动物细胞中，通过融合到异源DNA结合域而靶向DNA时抑制转录，（ii）特异性地与TIF1 β相互作用，但不与TIF1 α或TIF1 γ相互作用。综上所述，这些结果表明TIF1 β是KRAB锌指蛋白三个不同亚家族的共同转录辅助抑制因子，并表明其转录抑制活性的分子机制具有高度保守性。
The Kruppel-associated box (KRAB) domain, originally identified as a 75-aa sequence present in numerous Kruppel-type zinc-finger proteins, is a potent DNA-binding-dependent transcriptional repression domain that is believed to function through interaction with the transcriptional intermediary factor 1 (TIF1) beta. On the basis of sequence comparison and phylogenetic analysis, we have recently defined three distinct subfamilies of KRAB domains. In the present study, individual members of each subfamily were tested for transcriptional repression and interaction with TIF1 beta and two other closely related family members (TIF1 alpha and TIF1 gamma). All KRAB variants were shown, (i) to repress transcription when targeted to DNA through fusion to a heterologous DNA-binding domain in mammalian cells, and (ii) to interact specifically with TIF1 beta, but not with TIF1 alpha Or TIF1 gamma. Taken together, these results implicate TIF1 beta as a common transcriptional corepressor for the three distinct subfamilies of KRAB zinc-finger proteins and suggest a high degree of conservation in the molecular mechanism underlying their transcriptional repression activity.