Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility.
Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility.
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DOI：
10.1186/s13072-015-0009-5
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发表时间：
2015
影响因子：
3.9
通讯作者：
Hardison RC
中科院分区：
文献类型：
--
作者：
Dogan N;Wu W;Morrissey CS;Chen KB;Stonestrom A;Long M;Keller CA;Cheng Y;Jain D;Visel A;Pennacchio LA;Weiss MJ;Blobel GA;Hardison RC
受调控的基因表达控制着生物体的发育，而调控模式的变化与复杂性状有关。因此，对增强子的准确预测对于进一步了解这些过程非常重要。表观遗传特征的全基因组测量，如组蛋白修饰和转录因子的占用，正在改善增强子的预测，但这些特征对预测准确性的贡献尚不清楚。鉴于造血转录因子TAL1对红细胞基因激活的重要性，我们基于TAL1的基因组占用率预测候选增强子并测量其活性。基于这些和其他研究的结果，评估了多个特征对增强子预测的贡献。tal1结合的DNA片段在培养细胞（79个中的39个，或56%）和转基因小鼠（66个中的43个，或65%）的瞬时转染中都有很高的活性增强子。TAL1或GATA1的结合信号水平并不能帮助区分TAL1结合的DNA片段是活性增强子还是非活性增强子，也不能区分与调节相关的组蛋白修饰的密度。对这项研究和其他研究（273个测试的预测增强子）的结果进行meta分析表明，在dna酶超敏感位点存在TAL1、GATA1、EP300、SMAD1、H3K4甲基化、H3K27ac和CAGE标签，可以最准确地预测增强子的活性，成功率超过80%，活性中位数增加了三倍。染色质可及性测定和组蛋白修饰H3K4me1和H3K27ac对发现增强子是敏感的，但它们有很高的假阳性率，除非转录因子占用也包括在内。TAL1、GATA1、SMAD1和EP300等关键转录因子的占用，以及转录的证据，提高了基于表观遗传特征的增强子预测的准确性。本文的在线版本（doi:10.1186/s13072-015-0009-5）包含补充材料，授权用户可以使用。
Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features. The online version of this article (doi:10.1186/s13072-015-0009-5) contains supplementary material, which is available to authorized users.
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影响因子：
12.3
作者：
Attanasio C;Reymond A;Humbert R;Lyle R;Kuehn MS;Neph S;Sabo PJ;Goldy J;Weaver M;Haydock A;Lee K;Dorschner M;Dermitzakis ET;Antonarakis SE;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
7
作者：
Gorkin DU;Lee D;Reed X;Fletez-Brant C;Bessling SL;Loftus SK;Beer MA;Pavan WJ;McCallion AS
通讯作者：
McCallion AS
影响因子：
20.3
作者：
Gregory, T;Yu, CN;Weiss, MJ
通讯作者：
Weiss, MJ
影响因子：
4.3
作者：
Erwin GD;Oksenberg N;Truty RM;Kostka D;Murphy KK;Ahituv N;Pollard KS;Capra JA
通讯作者：
Capra JA
DOI：
10.4161/jkst.23931
发表时间：
2013-07-01
期刊：
JAK-STAT
影响因子：
--
作者：
Au-Yeung N;Mandhana R;Horvath CM
通讯作者：
Horvath CM