增强子预测及靶向测序技术研究进展

doi:10.16431/j.cnki.1671-7236.2019.05.007

Abstract

Abstract:

Enhancers have traditionally been defined as genomic cis-regulatory sequences that regulate the transcription of one or more genes independently of the transcription direction and relative position to the target promoter.The activity of enhancers plays a key regulatory role in growth and development,gene expression diversity,evolution and human disease occurrence.Therefore,understanding the functional characteristics of enhancers will not only help us understand the space-time specificity of gene expression,but also help us finally reveal the key biological issues such as cells differentiate,species evolve,and non-coding region variation leads to disease.With the rapid development of high-throughput sequencing technology,the methods and tools for the prediction,identification and functional annotation of enhancers also show diversity,including sequence motif analysis,in vivo binding sites of transcription factors and cofactors,feature chromatin and histone modification,large-scale parallel enhancer analysis,and CRSPR related technologies.This article reviews six methods of enhancer identification,recognition and prediction based on high-throughput sequencing technology at the whole genome level using regulatory factor binding sites,chromatin accessibility,histone modification,enhancer-promoter interaction,eRNAs and in vitro luciferase,and expounds in detail how to target enhancer research using gene editing technology.Finally,the role of enhancer research and individual research enhancer at the whole genome level is prospected,and the methods of targeted prediction of enhancer are described in detail,and the advantages and limitations of each method are compared,providing a reference for further research in this field.

Key words: enhancer; high-throughput sequencing; targeted sequencing; CRISPR

CLC Number:

WANG Jin, ZHAO Zhengwei, MA Lina, MA Qing. Research Progress on Enhancer Forecast and Targeted Sequencing Technology[J]. China Animal Husbandry & Veterinary Medicine, 2019, 46(5): 1308-1315.

References

[1] FULCO C P,MUNSCHAUER M,ANYOHA R,et al.Systematic mapping of functional enhancer-promoter connections with CRISPR interference[J].Science,2016,354(6313):769-773.
[2] BANERJI J,RUSCONI S,SCHAFFNER W.Expression of a β-globin gene is enhanced by remote SV40 DNA sequences[J].Cell,1981,27(2):299-308.
[3] BULGER M,GROUDINE M.Functional and mechanistic diversity of distal transcription enhancers[J].Cell,2011,144(3):327-339.
[4] LAMBERT S A,JOLMA A,CAMPITELLI L F,et al.The human transcription factors[J].Cell,2018,172(4):650-665.
[5] BUECKER C,WYSOCKA J.Enhancers as information integration hubs in development:Lessons from genomics[J].Trends Genet,2012,28(6):276-284.
[6] STADHOUDERS R,VIDAL E,SERRA F,et al.Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming[J]. Nature Genetics,2018,50(2):238-249.
[7] LAM D D,DE SOUZA F S J,NASIF S,et al.Partially redundant enhancers cooperatively maintain mammalian pomc expression above a critical functional threshold[J].PLoS Genetics,2015,11(2):e1004935.
[8] RIBARSKA T,GILFILLAN G D.Native chromatin immunoprecipitation-sequencing (ChIP-Seq) from low cell numbers[J].Methods in Molecular Biology,2018,1689:157-166.
[9] UMEYAMA T,ITO T.DMS-Seq for in vivo genome-wide mapping of protein-DNA interactions and nucleosome centers[J].Cell Reports,2017,21(1):289-300.
[10] VISEL A,BLOW M J,LI Z,et al.ChIP-seq accurately predicts tissue-specific activity of enhancers[J].Nature,2009,457(7231):854-858.
[11] RHEE H,PUGH B.Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide resolution[J].Cell,2011,147(6):1408-1419.
[12] RHEE H S,CLOSSER M,GUO Y,et al.Expression of terminal effector genes in mammalian neurons is maintained by a dynamic relay of transient enhancers[J].Neuron,2011,92(6):1252-1265.
[13] VAN S B,HENIKOFF S.Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase[J].Nature Biotechnology,2000,18(4):424-428.
[14] CEBALLOS-CHÁVEZ M,SUBTIL-RODRíGUEZ A,GIANNOPOULOU E G,et al.The chromatin remodeler CHD8 is required for activation of progesterone receptor-dependent enhancers[J].PLoS Genetics,2015,11(4):e1005174.
[15] BOYLE A P,DAVIS S,SHULHA H P,et al.High-resolution mapping and characterization of open chromatin across the genome[J].Cell,2008,132(2):311-322.
[16] YUAN G C,LIU Y J,DION M F,et al.Genome-scale identification of nucleosome positions in S.cerevisiae[J].Science,2005,309(5734):626-630.
[17] LEBLANC B,RODRIGUE S.DNA-Protein Interactions[M].New York:Humana Press,2015.
[18] PIQUEREGI R,DEGNER J F,PAI A A,et al.Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data[J].Genome Research,2011,21(3):447-455.
[19] GONZÁLEZ ALVARO J,MANU S,LESLIE C S.Early enhancer establishment and regulatory locus complexity shape transcriptional programs in hematopoietic differentiation[J].Nature Genetics,2015,47(11):1249-1259.
[20] LAI Y T,DEEM K D,BORRAS-CASTELLS F,et al.Enhancer identification and activity evaluation in the red flour beetle, Tribolium castaneum[J].Development,2018,7:160663.
[21] KOUZARIDES T.Chromatin modifications and their function[J].Cell,2007,128(4):693-705.
[22] HEINTZMAN N D N.Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome[J].Nature Genetics,2007,39(3):311-318.
[23] HEINTZMAN N D,HON G C,HAWKINS R D,et al.Histone modifications at human enhancers reflect global cell-type-specific gene expression[J].Nature,2009,459(7243):108-112.
[24] HAWKINS R D,HON G C,REN B.Next-generation genomics:An integrative approach[J].Nature Reviews Genetics,2010,11(7):476-486.
[25] RADAIGLESIAS A,BAJPAI R,SWIGUT T,et al.A unique chromatin signature uncovers early developmental enhancers in humans[J].Nature,2011,470(7333):279-283.
[26] WHYTE W,ORLANDO D,HNISZ D,et al.Master transcription factors and mediator establish super-enhancers at key cell identity genes[J].Cell,2013,153(2):307-319.
[27] JIN F,LI Y,DIXON J R,et al.A high-resolution map of the three-dimensional chromatin interactome in human cells[J].Nature,2013,503(7475):290-294.
[28] DEKKER J.Two ways to fold the genome during the cell cycle:Insights obtained with chromosome conformation capture[J]. Epigenetics & Chromatin,2014,7(1):25.
[29] KIM J H,TITUS K R,GONG W,et al.5C-ID:Increased resolution chromosome-conformation-capture-carbon-copy with in situ 3C and double alternating primer design[J].Methods,2018,142:39-46.
[30] LIEBERMAN-AIDEN E,VAN BERKUM N L,WILLIAMS L,et al.Comprehensive mapping of long-range interactions reveals folding principles of the human genome[J].Science,2009,326(5950):289-293.
[31] DOYLE B,FUDENBERG G,IMAKAEV M,et al.Chromatin loops as allosteric modulators of enhancer-promoter interactions[J].PLoS Computational Biology,2014,10(10):e1003867.
[32] BARRANGOU R.The roles of CRISPR-Cas systems in adaptive immunity and beyond[J].Current Opinion in Immunology,2015,32:36-41.
[33] PUC J,KOZBIAL P,LI W,et al.Ligand-dependent enhancer activation regulated by topoisomerase-Ⅰactivity[J].Cell,2015,160(3):367-380.
[34] DANKO C G,HYLAND S L,CORE L J,et al.Identification of active transcriptional regulatory elements from GRO-seq data[J].Nature Methods,2015,12(5):433-438.
[35] LAM M T,CHO H,LESCH H P,et al.Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription[J].Nature,2013,498(7455):511-515.
[36] MOUSAVI K,ZARE H,DELL'ORSO S,et al.eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci[J].Molecular Cell,2013,51(5):606-617.
[37] NOJIMA T,GOMES T,GROSSO A R F,et al.Mammalian NET-Seq reveals genome-wide nascent transcription coupled to RNA processing[J].Cell,2015,161(3):526-540.
[38] KIM T K,HEMBERG M,GRAY J M,et al.Widespread transcription at neuronal activity-regulated enhancers[J].Nature,2010,465(7295):182-187.
[39] MELNIKOV A,MURUGAN A,ZHANG X,et al.Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay[J].Nature Biotechnology,2012,30(3):271-277.
[40] ERNST J,MELNIKOV A,ZHANG X,et al.Genome-scale high-resolution mapping of activating and repressive nucleotides in regulatory regions[J].Nature Biotechnology,2016,34(11):1180-1190.
[41] ARNOLD C D,GERLACH D,STELZER C,et al.Genome-wide quantitative enhancer activity maps identified by STARR-seq[J].Science,2013,339(6123):1074-1077.
[42] LEDFORD H.CRISPR,the disruptor[J].Nature,2015,522(7554):20-24.
[43] GILBERT L A,HORLBECK M A,ADAMSON B,et al.Genome-scale CRISPR-mediated control of gene repression and activation[J].Cell,2014,159(3):647-661.
[44] KORKMAZ G,LOPES R,UGALDE A P,et al.Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9[J].Nature Biotechnology,2016,34(2):192-198.
[45] CANVER M C,SMITH E C,SHER F,et al.BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesus[J]. Nature,2015,527(7577):192-197.
[46] MCKENNA A,FINDLAY G M,GAGNON J A,et al.Whole organism lineage tracing by combinatorial and cumulative genome editing[J]. Science,2016,353(6298):462-473.
[47] CONG L,RAN F A,COX D,et al.Multiplex genome engineering using CRISPR/Cas systems[J].Science,2013,339(6121):819-823.
[48] GROSCHEL S,SANDERS M A,HOOGENBOEZEM R,et al.A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia[J].Cell,2014,157(2):369-381.
[49] ZHOU H Y,KATSMAN Y,DHALIWAL N K,et al.A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential[J].Genes & Development,2014,28(24):2699-2711.
[50] CANVER M C,BAUER D E,DASS A,et al.Characterization of genomic deletion efficiency mediated by clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells[J].Journal of Biological Chemistry,2014,289(31):21312-21324.
[51] QI L S,LARSON M H,GILBERT L A,et al.Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression[J].Cell,2013,152(5):1173-1183.
[52] THAKORE P I,D'IPPOLITO A M,SONG L,et al.Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements[J].Nature Methods,2015,12(12):1143-1149.
[53] KEARNS N A,PHAM H,TABAK B,et al.Functional annotation of native enhancers with a Cas9-histone demethylase fusion[J].Nature Methods,2015,12(5):401-403.
[54] WHYTE W A,BILODEAU S,ORLANDO D A,et al.Enhancer decommissioning by LSD1 during embryonic stem cell differentiation[J].Nature,2012,482(7384):221-225.
[55] GAO X,TSANG J C H,GABA F,et al.Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers[J].Nucleic Acids Research,2014,42(20):e155.
[56] HILTON I B,D'IPPOLITO A M,VOCKLEY C M,et al.Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers[J].Nature Biotechnology,2015,33(5):510-517.
[57] XIE S,DUAN J,LI B,et al.Multiplexed engineering and analysis of combinatorial enhancer activity in single cells[J].Molecular Cell,2017,66(2):285-299.

Research Progress on Enhancer Forecast and Targeted Sequencing Technology

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