{"title":"辨别 DNA 序列、形状和灵活性在果蝇转录因子识别中的作用。","authors":"Smrithi Murthy, Upalabdha Dey, Kaushika Olymon, Eshan Abbas, Venkata Rajesh Yella* and Aditya Kumar*, ","doi":"10.1021/acschembio.4c00202","DOIUrl":null,"url":null,"abstract":"<p >The precise spatial and temporal orchestration of gene expression is crucial for the ontogeny of an organism and is mainly governed by transcription factors (TFs). The mechanism of recognition of cognate sites amid millions of base pairs in the genome by TFs is still incompletely understood. In this study, we focus on DNA sequence composition, shape, and flexibility preferences of 28 quintessential TFs from <i>Drosophila melanogaster</i> that are critical to development and body patterning mechanisms. Our study finds that TFs exhibit distinct predilections for DNA shape, flexibility, and sequence compositions in the proximity of transcription factor binding sites (TFBSs). Notably, certain zinc finger proteins prefer GC-rich areas with less negative propeller twist, while homeodomains mainly seek AT-rich regions with a more negative propeller twist at their sites. Intriguingly, while numerous cofactors share similar binding site preferences and bind closer to each other in the genome, some cofactors that have different preferences bind farther apart. These findings shed light on TF DNA recognition and provide novel insights into possible cofactor binding and transcriptional regulation mechanisms.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discerning the Role of DNA Sequence, Shape, and Flexibility in Recognition by Drosophila Transcription Factors\",\"authors\":\"Smrithi Murthy, Upalabdha Dey, Kaushika Olymon, Eshan Abbas, Venkata Rajesh Yella* and Aditya Kumar*, \",\"doi\":\"10.1021/acschembio.4c00202\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The precise spatial and temporal orchestration of gene expression is crucial for the ontogeny of an organism and is mainly governed by transcription factors (TFs). The mechanism of recognition of cognate sites amid millions of base pairs in the genome by TFs is still incompletely understood. In this study, we focus on DNA sequence composition, shape, and flexibility preferences of 28 quintessential TFs from <i>Drosophila melanogaster</i> that are critical to development and body patterning mechanisms. Our study finds that TFs exhibit distinct predilections for DNA shape, flexibility, and sequence compositions in the proximity of transcription factor binding sites (TFBSs). Notably, certain zinc finger proteins prefer GC-rich areas with less negative propeller twist, while homeodomains mainly seek AT-rich regions with a more negative propeller twist at their sites. Intriguingly, while numerous cofactors share similar binding site preferences and bind closer to each other in the genome, some cofactors that have different preferences bind farther apart. These findings shed light on TF DNA recognition and provide novel insights into possible cofactor binding and transcriptional regulation mechanisms.</p>\",\"PeriodicalId\":11,\"journal\":{\"name\":\"ACS Chemical Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acschembio.4c00202\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Biology","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschembio.4c00202","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
基因表达在空间和时间上的精确协调对生物体的本体发育至关重要,主要由转录因子(TFs)控制。转录因子识别基因组中数百万个碱基对中的同源位点的机制尚未完全明了。在这项研究中,我们重点研究了黑腹果蝇中对发育和身体模式化机制至关重要的 28 种典型 TFs 的 DNA 序列组成、形状和灵活性偏好。我们的研究发现,在转录因子结合位点(TFBS)附近,转录因子对 DNA 的形状、灵活性和序列组成表现出不同的偏好。值得注意的是,某些锌指蛋白偏好负螺旋桨扭转较小的富含 GC 的区域,而同源结构域主要寻找富含 AT 的区域,其结合位点的负螺旋桨扭转较大。耐人寻味的是,虽然许多辅助因子具有相似的结合位点偏好,并且在基因组中彼此结合得较近,但一些具有不同偏好的辅助因子却结合得较远。这些发现揭示了 TF DNA 的识别,并为可能的辅助因子结合和转录调控机制提供了新的见解。
Discerning the Role of DNA Sequence, Shape, and Flexibility in Recognition by Drosophila Transcription Factors
The precise spatial and temporal orchestration of gene expression is crucial for the ontogeny of an organism and is mainly governed by transcription factors (TFs). The mechanism of recognition of cognate sites amid millions of base pairs in the genome by TFs is still incompletely understood. In this study, we focus on DNA sequence composition, shape, and flexibility preferences of 28 quintessential TFs from Drosophila melanogaster that are critical to development and body patterning mechanisms. Our study finds that TFs exhibit distinct predilections for DNA shape, flexibility, and sequence compositions in the proximity of transcription factor binding sites (TFBSs). Notably, certain zinc finger proteins prefer GC-rich areas with less negative propeller twist, while homeodomains mainly seek AT-rich regions with a more negative propeller twist at their sites. Intriguingly, while numerous cofactors share similar binding site preferences and bind closer to each other in the genome, some cofactors that have different preferences bind farther apart. These findings shed light on TF DNA recognition and provide novel insights into possible cofactor binding and transcriptional regulation mechanisms.
期刊介绍:
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.