Genome-wide footprinting: ready for prime time?
Genome-wide footprinting: ready for prime time?
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DOI：
10.1038/nmeth.3766
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发表时间：
2016-03
期刊：
影响因子：
48
通讯作者：
Hager, Gordon L.
中科院分区：
文献类型：
--
作者：
Sung, Myong-Hee;Baek, Songjoon;Hager, Gordon L.
高通量测序技术已经允许许多基因座水平的分子生物学测定成为全基因组分析方法。DNA裂解酶如DNA酶I已被用于探测可接近的染色质。可及区域包含功能调节位点，包括启动子、绝缘子和增强子。DNase-seq文库的深度测序和切割图谱的计算分析已被用于在核苷酸水平上推断基因组中的蛋白质占有率，这是一种被称为“数字基因组足迹”的方法。该方法已被提出作为通过染色质免疫沉淀随后测序（ChIP-seq）分析转录因子（TF）的有吸引力的替代方案，并且在理论上它应该克服抗体问题、分辨率差和批次效应。最近的报道指出了基于DNA酶的基因组足迹法的局限性，并对可检测蛋白质占用的范围提出了质疑，特别是对于具有短寿命染色质结合的TF。基因组学界正在努力解决基因组足迹的效用问题，并正在重新评估所提出的方法的可靠性。在这里，我们总结了最近的报告中出现的共识以及不同的观点，我们描述了基因组足迹的剩余问题和障碍。
High-throughput sequencing technologies have allowed many gene locus–level molecular biology assays to become genome-wide profiling methods. DNA-cleaving enzymes such as DNase I have been used to probe accessible chromatin. The accessible regions contain functional regulatory sites, including promoters, insulators and enhancers. Deep sequencing of DNase-seq libraries and computational analysis of the cut profiles have been used to infer protein occupancy in the genome at the nucleotide level, a method introduced as ‘digital genomic footprinting’. The approach has been proposed as an attractive alternative to the analysis of transcription factors (TFs) by chromatin immunoprecipitation followed by sequencing (ChIP-seq), and in theory it should overcome antibody issues, poor resolution and batch effects. Recent reports point to limitations of the DNase-based genomic footprinting approach and call into question the scope of detectable protein occupancy, especially for TFs with short-lived chromatin binding. The genomics community is grappling with issues concerning the utility of genomic footprinting and is reassessing the proposed approaches in terms of robust deliverables. Here we summarize the consensus as well as different views emerging from recent reports, and we describe the remaining issues and hurdles for genomic footprinting.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
64.8
作者：
CHURCH, GM;EPHRUSSI, A;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
30.8
作者：
John S;Sabo PJ;Thurman RE;Sung MH;Biddie SC;Johnson TA;Hager GL;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS