奥地利维也纳生物中心Alexander Stark研究团队揭示了果蝇转录共抑制因子和增强子之间广泛的调控特异性。2023年7月14日，《科学》杂志发表了这一研究成果。

研究人员报告了果蝇中的大多数增强子只能被一部分共抑制因子（CoR）抑制，而且按CoR敏感性分类的增强子显示出不同的染色质特征、功能、转录因子（TF）基序和结合。不同的TF基团使增强子对特定的CoR更耐受或更敏感，研究人员通过基团突变和添加证明了这一点。

这些CoR-增强子的兼容性构成了另一层调控特异性，允许在较近的基因组距离内进行不同的调控，并表明了不同的转录抑制机制。

据了解，基因表达受转录的精确激活和抑制控制。抑制由特化的TF介导，即使存在激活线索，它们也会招募CoR来抑制转录。然而，CoR是否能优势沉默所有增强子或显示出不同的特异性尚不清楚。

附：英文原文

Title: Widespread regulatory specificities between transcriptional co-repressors and enhancers in Drosophila

Author: Jelle Jacobs, Michaela Pagani, Christoph Wenzl, Alexander Stark

Issue&Volume: 2023-07-14

Abstract: Gene expression is controlled by the precise activation and repression of transcription. Repression is mediated by specialized transcription factors (TFs) that recruit co-repressors (CoRs) to silence transcription, even in the presence of activating cues. However, whether CoRs can dominantly silence all enhancers or display distinct specificities is unclear. In this work, we report that most enhancers in Drosophila can be repressed by only a subset of CoRs, and enhancers classified by CoR sensitivity show distinct chromatin features, function, TF motifs, and binding. Distinct TF motifs render enhancers more resistant or sensitive to specific CoRs, as we demonstrate by motif mutagenesis and addition. These CoR-enhancer compatibilities constitute an additional layer of regulatory specificity that allows differential regulation at close genomic distances and is indicative of distinct mechanisms of transcriptional repression.

DOI: adf6149

Source: https://www.science.org/doi/10.1126/science.adf6149