Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.
Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.
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DOI：
10.1101/gad.252122.114
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发表时间：
2015-01-01
影响因子：
10.5
通讯作者：
Lai EC
中科院分区：
文献类型：
--
作者：
Dai Q;Ren A;Westholm JO;Duan H;Patel DJ;Lai EC
BEN结构域被认为是一类新的保守的DNA结合结构域。果蝇基因组编码三种仅携带单个BEN结构域的蛋白质（“BEN-solo”因子）;即，不敏感（Insv）、Bsg 25 A（Elba 1）和CG 9883（Elba 2）。Dai等人鉴定了这三种果蝇BEN-solo蛋白的不同和重叠的功能特性，在它们对基因调控和发育的贡献中引入了意想不到的复杂性。BEN（BANP，E5 R，NAC 1）结构域是近年来发现的一类新的保守的DNA结合结构域。果蝇基因组编码三种仅携带单个BEN结构域的蛋白质（“BEN-solo”因子）;即，不敏感（Insv）、Bsg 25 A（Elba 1）和CG 9883（Elba 2）。Insv同源二聚体优先结合整个基因组中的CCAATTGG回文序列以介导转录抑制，而Bsg 25 A和Elba 2与其专性衔接子Elba 3异源三聚化（即，ELBA复合物），以识别Fab-7绝缘子中的CCAATAAG基序。虽然这些数据表明BEN-solo蛋白具有不同的DNA结合特性，但我们进行了报告基因测定，表明Bsg 25 A和Elba 2都可以有效地单独识别Insv共有位点。我们通过解决与Insv位点复合的Bsg 25 A的结构证实了这一点，这表明BEN的关键方面：DNA识别策略在这些蛋白质之间是相似的。我们接下来表明，Insv和ELBA蛋白都有能力通过Insv共有序列介导转录抑制，但ELBA复合物似乎对ELBA位点具有选择性。反过来，全基因组分析表明，Insv表现出显着的共结合I类绝缘子元件，表明它也可能有助于绝缘子功能。事实上，我们观察到丰富的Insv结合内的Hox复合物与I类绝缘体，其中许多承担Insv的共识网站大量重叠。此外，Insv与I类绝缘子因子CP 190共免疫沉淀。最后，我们观察到，Insv港口独家活动之间飞BEN独奏因素方面的调节Notch介导的细胞命运的选择在周围神经系统。BEND 6是一种哺乳动物BEN-solo因子，它保留了Insv的Notch辅阻遏物功能，但不保留其结合Insv共有位点的能力，这种体内活性被BEND 6概括。总之，我们的数据定义了一系列共同的和独特的生化和功能特性的这个新的转录因子家族。
The BEN domain is recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain (“BEN-solo” factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Dai et al. identify both distinct and overlapping functional properties of these three Drosophila BEN-solo proteins, introducing unexpected complexity in their contributions to gene regulation and development. Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain (“BEN-solo” factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional properties of this new family of transcription factors.
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影响因子：
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作者：
Li M;Belozerov VE;Cai HN
通讯作者：
Cai HN
影响因子：
4.5
作者：
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White KP
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通讯作者：
Posakony, JW
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5.3
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通讯作者：
Chattopadhyay, S
影响因子：
4.7
作者：
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通讯作者：
Mackler, SA