Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes.
Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes.
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DOI：
10.1101/gr.139360.112
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发表时间：
2012-11
期刊：
影响因子：
7
通讯作者：
McCallion AS
中科院分区：
文献类型：
--
作者：
Gorkin DU;Lee D;Reed X;Fletez-Brant C;Bessling SL;Loftus SK;Beer MA;Pavan WJ;McCallion AS
我们采取全面的方法来研究黑素细胞中基因表达的调控，从ChIP-seq促进的大规模增强子发现开始;在计算机，体外和体内进行严格的验证;最后使用机器学习来阐明具有全基因组预测能力的调控词汇。我们通过ChIP-seq确定了小鼠基因组中2489个推定的黑素细胞增强子位点，用于EP 300和H3 K4 me 1。我们证明，这些推定的增强子是进化上的限制，丰富的序列基序预测结合关键的黑素细胞转录因子，位于黑素细胞生物学相关的基因附近，并能够驱动报告基因表达的黑素细胞在文化（86%; 43/50）和转基因斑马鱼（70%; 7/10）。接下来，使用这些推定的增强子的序列作为监督机器学习算法的训练集，我们开发了一个预测黑素细胞增强子功能的6聚体词汇表。最后，我们证明了这个词汇在小鼠和人类基因组中都具有全基因组的预测能力。这项研究提供了深入了解黑素细胞中基因表达的调控，并展示了一个强大的方法来研究可应用于其他细胞类型的调控序列。
We take a comprehensive approach to the study of regulatory control of gene expression in melanocytes that proceeds from large-scale enhancer discovery facilitated by ChIP-seq; to rigorous validation in silico, in vitro, and in vivo; and finally to the use of machine learning to elucidate a regulatory vocabulary with genome-wide predictive power. We identify 2489 putative melanocyte enhancer loci in the mouse genome by ChIP-seq for EP300 and H3K4me1. We demonstrate that these putative enhancers are evolutionarily constrained, enriched for sequence motifs predicted to bind key melanocyte transcription factors, located near genes relevant to melanocyte biology, and capable of driving reporter gene expression in melanocytes in culture (86%; 43/50) and in transgenic zebrafish (70%; 7/10). Next, using the sequences of these putative enhancers as a training set for a supervised machine learning algorithm, we develop a vocabulary of 6-mers predictive of melanocyte enhancer function. Lastly, we demonstrate that this vocabulary has genome-wide predictive power in both the mouse and human genomes. This study provides deep insight into the regulation of gene expression in melanocytes and demonstrates a powerful approach to the investigation of regulatory sequences that can be applied to other cell types.
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影响因子：
2.7
作者：
Degenhardt KR;Milewski RC;Padmanabhan A;Miller M;Singh MK;Lang D;Engleka KA;Wu M;Li J;Zhou D;Antonucci N;Li L;Epstein JA
通讯作者：
Epstein JA
影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
DOI：
10.1073/pnas.1016959108
发表时间：
2011-04-05
影响因子：
11.1
作者：
He, Aibin;Kong, Sek Won;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
4.3
作者：
Cronin JC;Wunderlich J;Loftus SK;Prickett TD;Wei X;Ridd K;Vemula S;Burrell AS;Agrawal NS;Lin JC;Banister CE;Buckhaults P;Rosenberg SA;Bastian BC;Pavan WJ;Samuels Y
通讯作者：
Samuels Y
影响因子：
4.3
作者：
Dutton-Regester, Ken;Hayward, Nicholas K.
通讯作者：
Hayward, Nicholas K.