Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors.
Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors.
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DOI：
10.1371/journal.pbio.2004526
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发表时间：
2018-05
期刊：
影响因子：
9.8
通讯作者：
van Essen D
中科院分区：
文献类型：
--
作者：
Ramos Pittol JM;Oruba A;Mittler G;Saccani S;van Essen D
真核生物中的基因表达由启动子和增强子区域的DNA序列控制，其与调节蛋白结合的可及性决定了其特定的活性模式。在这里，我们确定蛋白质Zbtb 7a作为一个因子所需的诱导性变化的可访问性驱动的转录因子（TF）。我们发现Zbtb 7a结合到基因组启动子和增强子的显著部分，包括核因子κ B（NFκB）p65和各种其他TF的许多靶基因。虽然Zbtb 7a结合不足以直接激活启动子，但需要它来实现TF依赖性控制可及性和正常基因表达。使用p65作为模型TF，我们表明，Zbtb 7a与启动子独立的客户TF结合。此外，预先结合的Zbtb 7a的存在下，可以指定启动子，是服从TF诱导的可及性的变化。因此，Zbtb 7a代表了广泛使用的启动子因子，其从其他TF转导信号以使得能够控制基因表达的可及性和调节。基因激活是由调节蛋白与控制每个基因的特定DNA序列结合驱动的。然而，这些序列并不总是可以在每种类型的细胞中结合，因此它们可接近性的差异可能是特定基因可以被激活的细胞类型范围的基础。虽然几个细胞过程可以改变这些序列的accessibility，它仍然是经常不清楚这些过程是如何直接作用于特定的基因。我们已经发现，Zbtb 7a蛋白在整个基因组中的许多基因调控序列附近结合，并且它使其他DNA结合蛋白能够触发其可及性的变化并激活附近的基因。然而，与许多其他控制基因激活的因素不同，Zbtb 7a单独的结合似乎不足以开启基因表达;相反，它的功能是激活基因所必需的，这些基因独立地被一组特定的转录因子（TF）结合，因此它可以被认为是“抑制”它们的基因调控活性。这意味着，在特定细胞类型中的任何基因上存在或不存在Zbtb 7a可能代表可以确定该基因是否能够被激活的方面之一。
Gene expression in eukaryotes is controlled by DNA sequences at promoter and enhancer regions, whose accessibility for binding by regulatory proteins dictates their specific patterns of activity. Here, we identify the protein Zbtb7a as a factor required for inducible changes in accessibility driven by transcription factors (TFs). We show that Zbtb7a binds to a significant fraction of genomic promoters and enhancers, encompassing many target genes of nuclear factor kappa B (NFκB) p65 and a variety of other TFs. While Zbtb7a binding is not alone sufficient to directly activate promoters, it is required to enable TF-dependent control of accessibility and normal gene expression. Using p65 as a model TF, we show that Zbtb7a associates with promoters independently of client TF binding. Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression. Gene activation is driven by the binding of regulatory proteins to the specific DNA sequences that control each gene. However, these sequences are not always accessible for binding in every type of cell, and so differences in their accessibility can underlie the range of cell types in which particular genes can be activated. Although several cellular processes can alter the accessibilities of these sequences, it is still often unclear how these processes are directed to act at specific genes. We have discovered that the protein Zbtb7a binds near numerous gene-regulatory sequences throughout the genome and that it enables other DNA-binding proteins to trigger changes in their accessibility and to activate nearby genes. However, unlike many other factors that control gene activation, the binding of Zbtb7a alone does not seem to be sufficient to switch on gene expression; instead, its function is required for activation of genes that are independently bound by a specific set of transcription factors (TFs), and it could therefore be considered to “transduce” their gene-regulatory activities. The implication of this is that the presence or absence of Zbtb7a at any gene in a particular cell type may represent one of the aspects that can determine whether that gene is able to be activated or not.
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影响因子：
12.3
作者：
Worsley Hunt R;Wasserman WW
通讯作者：
Wasserman WW
影响因子：
10.5
作者：
Iwafuchi-Doi M;Zaret KS
通讯作者：
Zaret KS
影响因子：
8
作者：
Davies, JM;Hawe, N;Zelent, A
通讯作者：
Zelent, A
影响因子：
16
作者：
Biddie SC;John S;Sabo PJ;Thurman RE;Johnson TA;Schiltz RL;Miranda TB;Sung MH;Trump S;Lightman SL;Vinson C;Stamatoyannopoulos JA;Hager GL
通讯作者：
Hager GL
DOI：
10.1126/science.aad3312
发表时间：
2016-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Masuda T;Wang X;Maeda M;Canver MC;Sher F;Funnell AP;Fisher C;Suciu M;Martyn GE;Norton LJ;Zhu C;Kurita R;Nakamura Y;Xu J;Higgs DR;Crossley M;Bauer DE;Orkin SH;Kharchenko PV;Maeda T
通讯作者：
Maeda T