人类基因调控进化的动力来自顺式和反式调控元件功能的分化。

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-04-10 DOI:10.1016/j.xgen.2024.100536
Tyler J Hansen, Sarah L Fong, Jessica K Day, John A Capra, Emily Hodges
{"title":"人类基因调控进化的动力来自顺式和反式调控元件功能的分化。","authors":"Tyler J Hansen, Sarah L Fong, Jessica K Day, John A Capra, Emily Hodges","doi":"10.1016/j.xgen.2024.100536","DOIUrl":null,"url":null,"abstract":"<p><p>Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (∼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie ∼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019363/pdf/","citationCount":"0","resultStr":"{\"title\":\"Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.\",\"authors\":\"Tyler J Hansen, Sarah L Fong, Jessica K Day, John A Capra, Emily Hodges\",\"doi\":\"10.1016/j.xgen.2024.100536\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (∼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie ∼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species.</p>\",\"PeriodicalId\":72539,\"journal\":{\"name\":\"Cell genomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2024-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019363/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell genomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xgen.2024.100536\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2024.100536","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

物种间的基因调控差异可能来自调控元件 DNA 序列顺式作用的局部变化,也可能来自调控环境的全局性反式作用变化。对这些机制如何驱动调控进化的理解一直受到识别跨作用变化的挑战的限制。我们提出了一种综合方法,利用转座酶可接触染色质与自转录活性调控区(ATAC-STARR)测序相结合的检测方法,直接鉴定人类和猕猴淋巴母细胞之间的顺式和反式差异调控元件。除了数以千计的顺式变化外,我们还发现了意想不到的反式变化数量(∼10,000),并表明顺式和反式元件表现出不同的序列差异和功能模式。我们进一步确定了导致37%反式差异的不同表达的转录因子,并追踪顺式变化如何产生级联反式变化。总之,我们发现大多数差异元素(67%)都经历了顺式和反式的变化,揭示了反式差异--单独或与顺式变化一起--在物种间调控差异中的重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.

Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (∼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie ∼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
7.10
自引率
0.00%
发文量
0
期刊最新文献
AI-empowered perturbation proteomics for complex biological systems. Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas. Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data. Single-cell multi-modal integrative analyses highlight functional dynamic gene regulatory networks directing human cardiac development. Analysis of single-cell CRISPR perturbations indicates that enhancers predominantly act multiplicatively.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1