回溯以飞跃：转录进入新纪元。
Looping back to leap forward: transcription enters a new era.
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94707, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94707, USA; Howard Hughes Medical Institute, CIRM Center of Excellence, Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA 94707, USA.
出版信息
Cell. 2014 Mar 27;157(1):13-25. doi: 10.1016/j.cell.2014.02.009.
Abstract
Comparative genome analyses reveal that organismal complexity scales not with gene number but with gene regulation. Recent efforts indicate that the human genome likely contains hundreds of thousands of enhancers, with a typical gene embedded in a milieu of tens of enhancers. Proliferation of cis-regulatory DNAs is accompanied by increased complexity and functional diversification of transcriptional machineries recognizing distal enhancers and core promoters and by the high-order spatial organization of genetic elements. We review progress in unraveling one of the outstanding mysteries of modern biology: the dynamic communication of remote enhancers with target promoters in the specification of cellular identity.
摘要
比较基因组分析表明，生物复杂性的规模不是由基因数量决定，而是由基因调控决定的。最近的研究表明，人类基因组可能包含数十万个增强子，而一个典型的基因则嵌入在数十个增强子的环境中。顺式调控 DNA 的增殖伴随着识别远端增强子和核心启动子的转录机器的复杂性和功能多样化的增加，以及遗传元件的高阶空间组织的增加。我们回顾了在揭示现代生物学的一个突出谜团方面的进展：远程增强子与目标启动子之间的动态通信，以确定细胞身份。
相似文献
1
Looping back to leap forward: transcription enters a new era.回溯以飞跃：转录进入新纪元。
Cell. 2014 Mar 27;157(1):13-25. doi: 10.1016/j.cell.2014.02.009.
2
Molecular architecture of enhancer-promoter interaction.增强子-启动子相互作用的分子结构。
Curr Opin Cell Biol. 2022 Feb;74:62-70. doi: 10.1016/j.ceb.2022.01.003. Epub 2022 Feb 12.
3
Architectural and Functional Commonalities between Enhancers and Promoters.增强子与启动子之间的结构和功能共性
Cell. 2015 Aug 27;162(5):948-59. doi: 10.1016/j.cell.2015.08.008.
4
Dynamic modulation of enhancer-promoter and promoter-promoter connectivity in gene regulation.基因调控中增强子-启动子和启动子-启动子连接的动态调节。
Bioessays. 2024 Sep;46(9):e2400101. doi: 10.1002/bies.202400101. Epub 2024 Jun 25.
5
Large distances separate coregulated genes in living embryos.活体胚胎中，调控基因的距离较大。
Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):15062-15067. doi: 10.1073/pnas.1908962116. Epub 2019 Jul 8.
6
Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors.通过转录因子和辅助因子实现的调控增强子-核心启动子通讯
Trends Genet. 2016 Dec;32(12):801-814. doi: 10.1016/j.tig.2016.10.003. Epub 2016 Nov 2.
7
Regulatory landscape of enhancer-mediated transcriptional activation.增强子介导的转录激活的调控格局。
Trends Cell Biol. 2024 Oct;34(10):826-837. doi: 10.1016/j.tcb.2024.01.008. Epub 2024 Feb 13.
8
Transcriptional enhancers and their communication with gene promoters.转录增强子及其与基因启动子的通讯。
Cell Mol Life Sci. 2021 Oct;78(19-20):6453-6485. doi: 10.1007/s00018-021-03903-w. Epub 2021 Aug 19.
9
New insights into promoter-enhancer communication mechanisms revealed by dynamic single-molecule imaging.动态单分子成像揭示的启动子-增强子通讯机制的新见解。
Biochem Soc Trans. 2021 Jun 30;49(3):1299-1309. doi: 10.1042/BST20200963.
10
Super-enhancers include classical enhancers and facilitators to fully activate gene expression.超级增强子包括经典增强子和促进子，以充分激活基因表达。
Cell. 2023 Dec 21;186(26):5826-5839.e18. doi: 10.1016/j.cell.2023.11.030. Epub 2023 Dec 14.
引用本文的文献
1
Endogenous Real Time Imaging Reveals Dynamic Chromosomal Mobility During Ligand-Mediated Transcriptional Burst Events.内源性实时成像揭示配体介导的转录爆发事件期间染色体的动态移动性。
bioRxiv. 2025 Aug 19:2025.08.18.670875. doi: 10.1101/2025.08.18.670875.
2
DNA Sequence Perplexity Reveals Evolutionarily Conserved Patterns in cis-Regulatory Regions Across Diverse Species.DNA序列复杂性揭示了不同物种顺式调控区域中进化上保守的模式。
Biochem Genet. 2025 Aug 21. doi: 10.1007/s10528-025-11231-y.
3
Current progress and future perspective of super-enhancers: a viable and effective bridge between the transcriptional apparatus and disease.超级增强子的当前进展与未来展望：转录装置与疾病之间可行且有效的桥梁
Front Genet. 2025 Jul 2;16:1611905. doi: 10.3389/fgene.2025.1611905. eCollection 2025.
4
The evolutionary foundations of transcriptional regulation in animals.动物转录调控的进化基础。
Nat Rev Genet. 2025 Jul 9. doi: 10.1038/s41576-025-00864-9.
5
Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.靶向肝癌中的超级增强子：从致病机制到临床应用
Front Pharmacol. 2025 Jun 18;16:1589455. doi: 10.3389/fphar.2025.1589455. eCollection 2025.
6
MYC Binding Near Transcriptional End Sites Regulates Basal Gene Expression, Read-Through Transcription, and Intragenic Contacts.MYC在转录末端位点附近的结合调控基础基因表达、通读转录和基因内接触。
Adv Sci (Weinh). 2025 May 30:e14601. doi: 10.1002/advs.202414601.
7
Temporally discordant chromatin accessibility and DNA demethylation define short- and long-term enhancer regulation during cell fate specification.时间上不一致的染色质可及性和DNA去甲基化定义了细胞命运决定过程中的短期和长期增强子调控。
Cell Rep. 2025 May 27;44(5):115680. doi: 10.1016/j.celrep.2025.115680. Epub 2025 May 9.
8
Probing the limits of cis-acting gene regulation using a model of allelic imbalance quantitative trait loci.利用等位基因不平衡数量性状位点模型探究顺式作用基因调控的极限。
PLoS Genet. 2025 Apr 30;21(4):e1011446. doi: 10.1371/journal.pgen.1011446. eCollection 2025 Apr.
9
Nonproteolytic ubiquitination regulates chromatin occupancy by the NCoR/SMRT/HDAC3 corepressor complex in MCF-7 breast cancer cells.非蛋白酶体泛素化调控MCF-7乳腺癌细胞中NCoR/SMRT/HDAC3共抑制复合物对染色质的占据。
Proc Natl Acad Sci U S A. 2025 May 6;122(18):e2502805122. doi: 10.1073/pnas.2502805122. Epub 2025 Apr 30.
10
Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration.心脏增强子：通向心脏再生调控机制的大门。
Semin Cell Dev Biol. 2025 Jun;170:103610. doi: 10.1016/j.semcdb.2025.103610. Epub 2025 Apr 10.
本文引用的文献
1
Single-molecule dynamics of enhanceosome assembly in embryonic stem cells.胚胎干细胞中增强子组装的单分子动力学。
Cell. 2014 Mar 13;156(6):1274-1285. doi: 10.1016/j.cell.2014.01.062.
2
Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.SWI/SNF 在急性白血病维持和增强子介导的 Myc 调控中的作用。
Genes Dev. 2013 Dec 15;27(24):2648-62. doi: 10.1101/gad.232710.113. Epub 2013 Nov 27.
3
Phosphorylation-regulated binding of RNA polymerase II to fibrous polymers of low-complexity domains.磷酸化调节 RNA 聚合酶 II 与低复杂度域纤维状聚合物的结合。
Cell. 2013 Nov 21;155(5):1049-1060. doi: 10.1016/j.cell.2013.10.033.
4
Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons.成纤维细胞向神经元直接重编程的层次机制。
Cell. 2013 Oct 24;155(3):621-35. doi: 10.1016/j.cell.2013.09.028.
5
Fine tuning of craniofacial morphology by distant-acting enhancers.远隔作用增强子对颅面形态的精细调控。
Science. 2013 Oct 25;342(6157):1241006. doi: 10.1126/science.1241006.
6
Topology of mammalian developmental enhancers and their regulatory landscapes.哺乳动物发育增强子的拓扑结构及其调控景观。
Nature. 2013 Oct 24;502(7472):499-506. doi: 10.1038/nature12753.
7
A high-resolution map of the three-dimensional chromatin interactome in human cells.人类细胞三维染色质互作组的高分辨率图谱。
Nature. 2013 Nov 14;503(7475):290-4. doi: 10.1038/nature12644. Epub 2013 Oct 20.
8
Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning.定量成像转录在活的果蝇胚胎中连接聚合酶活性与模式形成。
Curr Biol. 2013 Nov 4;23(21):2140-5. doi: 10.1016/j.cub.2013.08.054. Epub 2013 Oct 17.
9
Live imaging of bicoid-dependent transcription in Drosophila embryos.果蝇胚胎中依赖 bicoid 的转录的实时成像。
Curr Biol. 2013 Nov 4;23(21):2135-9. doi: 10.1016/j.cub.2013.08.053. Epub 2013 Oct 17.
10
Structural insights into transcription initiation by RNA polymerase II.RNA 聚合酶 II 转录起始的结构见解。
Trends Biochem Sci. 2013 Dec;38(12):603-11. doi: 10.1016/j.tibs.2013.09.002. Epub 2013 Oct 11.
Zotero 插件