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研究转录增强子:奠基者谬误、验证蔓延和其他偏见。

Studying Transcriptional Enhancers: The Founder Fallacy, Validation Creep, and Other Biases.

机构信息

Department of Biochemistry, University at Buffalo-State University of New York, Buffalo, NY, USA; NY State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA; Department of Biological Sciences, University at Buffalo-State University of New York, Buffalo, NY, USA; Department of Biomedical Informatics, University at Buffalo-State University of New York, Buffalo, NY, USA; Department of Molecular and Cellular Biology and Program in Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

出版信息

Trends Genet. 2019 Feb;35(2):93-103. doi: 10.1016/j.tig.2018.11.004. Epub 2018 Dec 13.

DOI:10.1016/j.tig.2018.11.004
PMID:30553552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6338480/
Abstract

Transcriptional enhancers play a major role in regulating metazoan gene expression. Recent developments in genomics and next-generation sequencing have accelerated and revitalized the study of this important class of sequence elements. Increased interest and attention, however, has also led to troubling trends in the enhancer literature. In this Opinion, I describe some of these issues and show how they arise from shifting and nonuniform enhancer definitions, and genome-era biases. I discuss how they can lead to interpretative errors and an unduly narrow focus on certain aspects of enhancer biology to the potential exclusion of others.

摘要

转录增强子在调节后生动物基因表达中起着重要作用。基因组学和下一代测序技术的最新发展加速并振兴了对这一重要序列元件类别的研究。然而,日益增长的兴趣和关注也导致了增强子文献中的一些令人不安的趋势。在本观点中,我描述了其中的一些问题,并展示了它们是如何由不断变化和不均匀的增强子定义以及基因组时代的偏见引起的。我讨论了它们如何导致解释性错误,并将注意力过分集中在增强子生物学的某些方面,而潜在地排除了其他方面。

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Regulatory genome annotation of 33 insect species.33 种昆虫的调控基因组注释。
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本文引用的文献

1
Decoding the noncoding genome via large-scale CRISPR screens.通过大规模 CRISPR 筛选来解码非编码基因组。
Curr Opin Genet Dev. 2018 Oct;52:70-76. doi: 10.1016/j.gde.2018.06.001. Epub 2018 Jun 15.
2
Enhancer Logic and Mechanics in Development and Disease.增强子逻辑与发育和疾病中的机制
Trends Cell Biol. 2018 Aug;28(8):608-630. doi: 10.1016/j.tcb.2018.04.003. Epub 2018 May 11.
3
Comprehensive Analysis of a cis-Regulatory Region Reveals Pleiotropy in Enhancer Function.顺式调控区的综合分析揭示了增强子功能的多效性。
Cell Rep. 2018 Mar 13;22(11):3021-3031. doi: 10.1016/j.celrep.2018.02.073.
4
Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation.评估增强子活动对基因表达的充分性和必要性,以及转录激活的机制。
Genes Dev. 2018 Feb 1;32(3-4):202-223. doi: 10.1101/gad.310367.117.
5
Widespread transcriptional pausing and elongation control at enhancers.广泛的转录暂停和延伸控制增强子。
Genes Dev. 2018 Jan 1;32(1):26-41. doi: 10.1101/gad.309351.117. Epub 2018 Jan 29.
6
Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers.双向转录起始标志可及染色质,并且不限于增强子。
Genome Biol. 2017 Dec 28;18(1):242. doi: 10.1186/s13059-017-1379-8.
7
Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability.由Trr和哺乳动物类COMPASS蛋白在增强子处催化的组蛋白H3K4单甲基化对于发育和生存能力而言并非必需。
Nat Genet. 2017 Nov;49(11):1647-1653. doi: 10.1038/ng.3965. Epub 2017 Oct 2.
8
Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation.Mll3和Mll4促进增强子RNA合成及启动子转录,且不依赖于H3K4单甲基化。
Mol Cell. 2017 May 18;66(4):568-576.e4. doi: 10.1016/j.molcel.2017.04.018. Epub 2017 May 5.
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The Evolving Definition of the Term "Gene".“基因”一词不断演变的定义。
Genetics. 2017 Apr;205(4):1353-1364. doi: 10.1534/genetics.116.196956.
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The Functionality and Evolution of Eukaryotic Transcriptional Enhancers.真核生物转录增强子的功能与进化
Adv Genet. 2016;96:143-206. doi: 10.1016/bs.adgen.2016.08.004. Epub 2016 Oct 13.