Stage-specific repression by the EKLF transcriptional activator
Stage-specific repression by the EKLF transcriptional activator
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DOI：
10.1128/mcb.24.23.10416-10424.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Bieker, JJ
中科院分区：
文献类型：
--
作者：
Chen, XY;Bieker, JJ
转录因子功能的动态变化可以通过转换其与辅激活子和辅抑制子的相互作用来介导。红系Kruppel样因子（EKLF）是一种红系细胞特异性转录因子，通过与CBP/p300和SWI/SNF蛋白的相互作用在β-珠蛋白基因激活中起关键作用。出乎意料的是，它还通过其锌指结构域与Sin 3A和组蛋白脱乙酰酶1（HDAC 1）辅阻遏物相互作用。我们现在发现，选定的点突变体可以解偶联激活和抑制，并且与Sin 3A/HDAC 1的相互作用或反式抑制不需要完整的手指结构。最有趣的是，EKLF抑制表现出阶段特异性，可逆的EKLF-Sin 3A相互作用在这一过程中发挥了关键作用。最后，我们已经找到了一个关键的赖氨酸残基，它既是CBP乙酰化的底物，也是Sin 3A相互作用所必需的。这些数据表明一个模型，即阶段的红细胞改变乙酰化状态的EKLF，并在指导其辅激活子-辅阻遏物的相互作用和下游转录的影响中发挥了关键作用。
Dynamic changes in transcription factor function can be mediated by switching its interaction with coactivators and corepressors. Erythroid Kruppel-like factor (EKLF) is an erythroid cell-specific transcription factor that plays a critical role in beta-globin gene activation via its interactions with CBP/p300 and SWI/SNF proteins. Unexpectedly, it also interacts with Sin3A and histone deacetylase 1 (HDAC1) corepressors via its zinc finger domain. We now find that selected point mutants can uncouple activation and repression and that an intact finger structure is not required for interactions with Sin3A/HDAC1 or for transrepression. Most intriguingly, EKLF repression exhibits stage specificity, with reversible EKLF-Sin3A interactions playing a key role in this process. Finally, we have located a key lysine residue that is both a substrate for CBP acetylation and required for Sin3A interaction. These data suggest a model whereby the stage of the erythroid cell alters the acetylation status of EKLF and plays a critical role in directing its coactivator-corepressor interactions and downstream transcriptional effects.