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Transcription factors specifically control change
Genes & Development ( IF 10.5 ) Pub Date : 2022-11-01 , DOI: 10.1101/gad.350308.122 Ellen V Rothenberg 1
Genes & Development ( IF 10.5 ) Pub Date : 2022-11-01 , DOI: 10.1101/gad.350308.122 Ellen V Rothenberg 1
Affiliation
Transcription factors are defined by their sequence-specific binding to DNA and by their selective impacts on gene expression, depending on specific binding sites. The factor binding motifs in the DNA should thus represent a blueprint of regulatory logic, suggesting that transcription factor binding patterns on the genome (e.g., measured by ChIP-seq) should indicate which target genes the factors are directly controlling. However, although genetic data confirm high impacts of transcription factor perturbation in embryology, transcription factors bind to far more sites than the number of genes they dynamically regulate, when measured by direct perturbation in a given cell type. Also, deletion of carefully chosen transcription factor binding sites often gives disappointingly weak results. In a new study in the previous issue of Genes & Development, Lo and colleagues (pp. 1079–1095) reconcile these contradictions by using an elegant experimental system to directly compare the roles of transcription factor–binding site interaction in gene regulation maintenance with roles of the same factor–site interactions in gene regulation through developmental change. They examine Oct4:Sox2 shared target genes under maintained versus reinduced pluripotency conditions within the same cell clone. The results show that the same factor–site interaction impacts can appear modest in assays in developmental steady-state but are far more important as regulatory catalysts of developmental change.
中文翻译:
转录因子专门控制变化
转录因子的定义是它们与 DNA 的序列特异性结合以及它们对基因表达的选择性影响,具体取决于特定的结合位点。因此,DNA 中的因子结合基序应该代表调节逻辑的蓝图,表明基因组上的转录因子结合模式(例如,通过 ChIP-seq 测量)应该表明因子直接控制哪些靶基因。然而,尽管遗传数据证实了胚胎学中转录因子扰动的高度影响,但当通过给定细胞类型中的直接扰动测量时,转录因子结合的位点远远超过它们动态调节的基因数量。此外,删除精心选择的转录因子结合位点通常会产生令人失望的微弱结果。在上一期的一项新研究中Genes & Development,Lo 及其同事(第 1079–1095 页)通过使用一个优雅的实验系统直接比较转录因子-结合位点相互作用在基因调控维持中的作用与相同因子-位点相互作用在基因中的作用来调和这些矛盾通过发展变化进行监管。他们在同一细胞克隆内的维持多能性和再诱导多能性条件下检查 Oct4:Sox2 共享靶基因。结果表明,相同的因子-位点相互作用影响在发育稳态的分析中可能显得适度,但作为发育变化的调节催化剂则更为重要。
更新日期:2022-11-01
中文翻译:
转录因子专门控制变化
转录因子的定义是它们与 DNA 的序列特异性结合以及它们对基因表达的选择性影响,具体取决于特定的结合位点。因此,DNA 中的因子结合基序应该代表调节逻辑的蓝图,表明基因组上的转录因子结合模式(例如,通过 ChIP-seq 测量)应该表明因子直接控制哪些靶基因。然而,尽管遗传数据证实了胚胎学中转录因子扰动的高度影响,但当通过给定细胞类型中的直接扰动测量时,转录因子结合的位点远远超过它们动态调节的基因数量。此外,删除精心选择的转录因子结合位点通常会产生令人失望的微弱结果。在上一期的一项新研究中Genes & Development,Lo 及其同事(第 1079–1095 页)通过使用一个优雅的实验系统直接比较转录因子-结合位点相互作用在基因调控维持中的作用与相同因子-位点相互作用在基因中的作用来调和这些矛盾通过发展变化进行监管。他们在同一细胞克隆内的维持多能性和再诱导多能性条件下检查 Oct4:Sox2 共享靶基因。结果表明,相同的因子-位点相互作用影响在发育稳态的分析中可能显得适度,但作为发育变化的调节催化剂则更为重要。