Solution structure and DNA-binding mode of the matrix attachment region-binding domain of the transcription factor SATB1 that regulates the T-cell maturation
Solution structure and DNA-binding mode of the matrix attachment region-binding domain of the transcription factor SATB1 that regulates the T-cell maturation
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DOI：
10.1074/jbc.m510933200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Yamasaki, K
中科院分区：
文献类型：
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作者：
Yamaguchi, H;Tateno, M;Yamasaki, K
SATB1 是一种转录调节因子，控制着免疫 T 细胞成熟所必需的基因表达。 SATB1 与 DNA 的核基质附着区域结合，在那里招募组蛋白脱乙酰酶并通过局部染色质重塑抑制转录。在这里，我们通过核磁共振波谱确定了人 SATB1 的基质附着区结合域的溶液结构，该结构域与人 SATB1 的 CUT DNA 结合域相似。该结构由5个α螺旋组成，其中N端4个的排列方式与肝细胞核因子6α的CUT结构域的四螺旋结构类似。通过 NMR 化学位移扰动分析和 SATB1 突变蛋白的表面等离子共振分析，发现 DNA 结合界面位于第三螺旋及其周围区域。使用沟特异性结合药物和甲基化 DNA 进行的表面等离子共振实验表明，该结构域从主沟侧识别 DNA。这些观察结果表明，SATB1 具有与 POU 特异性 DNA 结合结构域相似的 DNA 结合模式，已知 POU 特异性 DNA 结合结构域与四螺旋 CUT 结构域具有结构相似性。
SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. SATB1 binds to the nuclear matrix attachment regions of DNA, where it recruits histone deacetylase and represses transcription through a local chromatin remodeling. Here we determined the solution structure of the matrix attachment region-binding domain, possessing similarity to the CUT DNA-binding domain, of human SATB1 by NMR spectroscopy. The structure consists of five alpha-helices, in which the N-terminal four are arranged similarly to the four-helix structure of the CUT domain of hepatocyte nuclear factor 6 alpha. By an NMR chemical shift perturbation analysis and by surface plasmon resonance analyses of SATB1 mutant proteins, an interface for DNA binding was revealed to be located at the third helix and the surrounding regions. Surface plasmon resonance experiments using groove-specific binding drugs and methylated DNAs indicated that the domain recognizes DNA from the major groove side. These observations suggested that SATB1 possesses a DNA-binding mode similar to that of the POU-specific DNA-binding domain, which is known to share structural similarity to the four-helix CUT domain.