Yeast transcription factor Msn2 binds to G4 DNA.
Yeast transcription factor Msn2 binds to G4 DNA.
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DOI：
10.1093/nar/gkad684
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发表时间：
2023-10-13
影响因子：
14.9
通讯作者：
Kim, Nayun
中科院分区：
文献类型：
--
作者：
Duy, Duong Long;Kim, Nayun
能够形成四链体或G4 DNA 的序列在启动子区域中普遍存在。从规范二级结构到非规范二级结构的转变显然调节了许多人类基因的转录。在芽殖酵母酿酒酵母中，我们鉴定了 37 个启动子中带有 G4 基序的基因，其中 20 个基因含有与 G4 基序重叠的应激反应元件 (STRE)。 STRE 是应激反应调节因子 Msn2 和 Msn4 的结合位点，Msn2 和 Msn4 是属于 C2H2 锌指蛋白家族的转录因子。我们在此表明，Msn2 通过其锌指结构域直接与 G4 DNA 结构结合，其解离常数与 STRE 结合相似，并且在应激条件下，Msn2 在酵母基因组中的 G4 DNA 形成位点处富集。对于大部分具有含 G4/STRE 启动子的基因，用 G4 配体处理会导致转录水平显着升高。这种转录升高在 msn2Δ msn4Δ 背景下大大减弱，并且当 G4 基序被破坏时部分减弱。综上所述，我们的数据表明，除了 STRE 之外，G4 DNA 可能是 Msn2 的另一个结合位点，并且 G4 DNA 的形成可能是酵母转录调控的重要元件。
Sequences capable of forming quadruplex or G4 DNA are prevalent in the promoter regions. The transformation from canonical to non-canonical secondary structure apparently regulates transcription of a number of human genes. In the budding yeast Saccharomyces cerevisiae, we identified 37 genes with a G4 motif in the promoters including 20 genes that contain stress response element (STRE) overlapping a G4 motif. STRE is the binding site of stress response regulators Msn2 and Msn4, transcription factors belonging to the C2H2 zinc-finger protein family. We show here that Msn2 binds directly to the G4 DNA structure through its zinc-finger domain with a dissociation constant similar to that of STRE-binding and that, in a stress condition, Msn2 is enriched at G4 DNA-forming loci in the yeast genome. For a large fraction of genes with G4/STRE-containing promoters, treating with G4-ligands led to significant elevations in transcription levels. Such transcriptional elevation was greatly diminished in a msn2Δ msn4Δ background and was partly muted when the G4 motif was disrupted. Taken together, our data suggest that G4 DNA could be an alternative binding site of Msn2 in addition to STRE, and that G4 DNA formation could be an important element of transcriptional regulation in yeast.
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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