TAF4/4b.TAF12 Displays a Unique Mode of DNA Binding and Is Required for Core Promoter Function of a Subset of Genes
TAF4/4b.TAF12 Displays a Unique Mode of DNA Binding and Is Required for Core Promoter Function of a Subset of Genes
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DOI：
10.1074/jbc.m109.011486
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发表时间：
2009-09-25
影响因子：
4.8
通讯作者：
Dikstein, Rivka
中科院分区：
文献类型：
--
作者：
Gazit, Kfir;Moshonov, Sandra;Dikstein, Rivka
聚合酶II转录机制中的主要核心启动子结合因子是TFIID，这是一种由TBP、TATA盒结合蛋白和13至14种TBP相关因子（TAF）组成的复合物。以前我们发现组蛋白H2 A样TAF旁系同源物TAF 4和TAF 4 b具有DNA结合活性。TAF 4/TAF 4 b DNA结合是否将TFIID引导至特定的核心启动子元件或促进TFIID结合至已建立的核心启动子元件尚不清楚。在这里，我们分析了TAF4b.TAF12 DNA结合的模式，并表明该复合物以高亲和力结合DNA。最佳结合所需的DNA长度类似于70 bp。虽然复合物显示弱序列偏好，但对于高亲和力结合，核苷酸组成不如DNA的长度重要。TAF 4野生型和DNA结合突变体的比较表达谱揭示了下调基因中共同的核心启动子特征，包括TATA盒和启动子。进一步检查该组的PEL 98基因显示TAF 4 DNA结合突变细胞中起始物活性和TFIID占用减少。这些发现表明，TAF 4/4 b-TAF 12的DNA结合促进了TFIID与基因子集的核心启动子的关联。
The major core promoter-binding factor in polymerase II transcription machinery is TFIID, a complex consisting of TBP, the TATA box-binding protein, and 13 to 14 TBP-associated factors (TAFs). Previously we found that the histone H2A-like TAF paralogs TAF4 and TAF4b possess DNA-binding activity. Whether TAF4/TAF4b DNA binding directs TFIID to a specific core promoter element or facilitates TFIID binding to established core promoter elements is not known. Here we analyzed the mode of TAF4b.TAF12 DNA binding and show that this complex binds DNA with high affinity. The DNA length required for optimal binding is similar to 70 bp. Although the complex displays a weak sequence preference, the nucleotide composition is less important than the length of the DNA for high affinity binding. Comparative expression profiling of wild-type and a DNA-binding mutant of TAF4 revealed common core promoter features in the down-regulated genes that include a TATA-box and an Initiator. Further examination of the PEL98 gene from this group showed diminished Initiator activity and TFIID occupancy in TAF4 DNA-binding mutant cells. These findings suggest that DNA binding by TAF4/4b-TAF12 facilitates the association of TFIID with the core promoter of a subset of genes.