Chen X, Bieker J J
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Mol Cell Biol. 2001 May;21(9):3118-25. doi: 10.1128/MCB.21.9.3118-3125.2001.
The erythroid cell-specific transcription factor erythroid Krüppel-like factor (EKLF) is an important activator of beta-globin gene expression. It achieves this by binding to the CACCC element at the beta-globin promoter via its zinc finger domain. The coactivators CBP and P300 interact with, acetylate, and enhance its activity, helping to explain its role as a transcription activator. Here we show that EKLF can also interact with the corepressors mSin3A and HDAC1 (histone deacetylase 1) through its zinc finger domain. When linked to a GAL4 DNA binding domain, full-length EKLF or its zinc finger domain alone can repress transcription in vivo. This repressive activity can be relieved by the HDAC inhibitor trichostatin A. Although recruitment of EKLF to a promoter is required to show repression, its zinc finger domain cannot bind directly to DNA and repress transcription simultaneously. In addition, the target promoter configuration is important for enabling EKLF to exhibit any repressive activity. These results suggest that EKLF may function in vivo as a transcription repressor and play a previously unsuspected additional role in regulating erythroid gene expression and differentiation.
红系细胞特异性转录因子红系Krüppel样因子（EKLF）是β-珠蛋白基因表达的重要激活因子。它通过其锌指结构域与β-珠蛋白启动子处的CACCC元件结合来实现这一点。共激活因子CBP和P300与它相互作用、使其乙酰化并增强其活性，这有助于解释它作为转录激活因子的作用。在此我们表明，EKLF还可通过其锌指结构域与共抑制因子mSin3A和HDAC1（组蛋白去乙酰化酶1）相互作用。当与GAL4 DNA结合结构域相连时，全长EKLF或其单独的锌指结构域均可在体内抑制转录。这种抑制活性可被HDAC抑制剂曲古抑菌素A解除。尽管要表现出抑制作用需要将EKLF募集到启动子，但它的锌指结构域不能直接结合DNA并同时抑制转录。此外，靶启动子构型对于使EKLF表现出任何抑制活性很重要。这些结果表明，EKLF在体内可能作为转录抑制因子发挥作用，并在调节红系基因表达和分化中发挥此前未被怀疑的额外作用。
