Identification and prediction of developmental enhancers in sea urchin embryos.
Identification and prediction of developmental enhancers in sea urchin embryos.
复制标题
海胆胚胎发育促进剂的鉴定与预测。
DOI：
10.1186/s12864-021-07936-0
复制
发表时间：
2021-10-19
期刊：
影响因子：
4.4
通讯作者：
Danko CG
中科院分区：
文献类型：
--
作者：
Arenas-Mena C;Miljovska S;Rice EJ;Gurges J;Shashikant T;Wang Z;Ercan S;Danko CG
发育调控基因的转录往往受多个顺式调控元件的调控。远端调控元件的鉴定和功能表征仍然具有挑战性，即使在像海胆这样易于驯化的模式生物中也是如此。我们评估了染色质可及性、转录和RNA聚合酶II用于预测海胆胚胎基因组区域增强子活性的能力。来自早期和晚期囊胚的ATAC-SEQ、PRO-SEQ和POL II CHIP-SEQ与海胆胚胎中可用的实验顺式调控分析进行了手动对比，特别关注已知具有不同胚胎区域之间不同部署的增强子和沉默功能的共同发育调控元件。使用三种功能基因组数据类型，机器学习模型被训练和测试，以分类和定量预测先前在体内用报告结构验证的数百个基因组区域的增强子活性。总体而言，染色质的可及性和转录对预测增强子活性有很大的作用。特别是对于启动子重叠的顺式调控元件，POL II的分布是预测囊胚中增强子活性的最佳指标。此外，对于启动子重叠的亚集，ATAC和PRO-SEQ的预测值是阶段相关的。这表明，导致转录激活的调控机制序列在胚胎发育过程中部署的发育基因调控体系的不同水平上具有明显的相关性。网上版载有补充材料，可在10.1186/s12864-021-07936-0查阅。
The transcription of developmental regulatory genes is often controlled by multiple cis-regulatory elements. The identification and functional characterization of distal regulatory elements remains challenging, even in tractable model organisms like sea urchins. We evaluate the use of chromatin accessibility, transcription and RNA Polymerase II for their ability to predict enhancer activity of genomic regions in sea urchin embryos. ATAC-seq, PRO-seq, and Pol II ChIP-seq from early and late blastula embryos are manually contrasted with experimental cis-regulatory analyses available in sea urchin embryos, with particular attention to common developmental regulatory elements known to have enhancer and silencer functions differentially deployed among embryonic territories. Using the three functional genomic data types, machine learning models are trained and tested to classify and quantitatively predict the enhancer activity of several hundred genomic regions previously validated with reporter constructs in vivo. Overall, chromatin accessibility and transcription have substantial power for predicting enhancer activity. For promoter-overlapping cis-regulatory elements in particular, the distribution of Pol II is the best predictor of enhancer activity in blastula embryos. Furthermore, ATAC- and PRO-seq predictive value is stage dependent for the promoter-overlapping subset. This suggests that the sequence of regulatory mechanisms leading to transcriptional activation have distinct relevance at different levels of the developmental gene regulatory hierarchy deployed during embryogenesis. The online version contains supplementary material available at 10.1186/s12864-021-07936-0.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
2.5
作者：
Arenas-Mena, Cesar;Cameron, R. Andrew;Davidson, Eric H.
通讯作者：
Davidson, Eric H.
DOI：
10.1038/s41580-018-0028-8
发表时间：
2018-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Haberle V;Stark A
通讯作者：
Stark A
影响因子：
64.8
作者：
Engreitz JM;Haines JE;Perez EM;Munson G;Chen J;Kane M;McDonel PE;Guttman M;Lander ES
通讯作者：
Lander ES
DOI：
10.1073/pnas.0806007105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Davidson, Eric H.;Levine, Michael S.
通讯作者：
Levine, Michael S.