Abstract
MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by CLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP's interactive HTML output groups and aligns significant motifs to ease interpretation. This protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis
Nature Communications Open Access 01 November 2022
-
PIF4 enhances DNA binding of CDF2 to co-regulate target gene expression and promote Arabidopsis hypocotyl cell elongation
Nature Plants Open Access 15 August 2022
-
Alcohol induced increases in sperm Histone H3 lysine 4 trimethylation correlate with increased placental CTCF occupancy and altered developmental programming
Scientific Reports Open Access 25 May 2022
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout





















References
Machanick, P. & Bailey, T.L. MEME-ChIP: motif analysis of large DNA datasets. Bioinformatics 27, 1696–1697 (2011).
Bailey, T.L. & Elkan, C.P. in Fitting a mixture model by expectation-maximization to discover motifs in biopolymers. (eds. Altman, R., Brutlag, D., Karp, P., Lathrop, R., & Searls, D.) Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology 28–36 (AAAI Press, 1994).
Bailey, T.L. DREME: Motif discovery in transcription factor ChIP-seq data. Bioinformatics 27, 1653–1659 (2011).
Bailey, T. & Machanick, P. Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res. 40, e128 (2012).
ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
Freeberg, M.A. et al. Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae. Genome Biol. 14, R13 (2013).
Kulakovskiy, I.V., Boeva, V.A., Favorov, A.V. & Makeev, V.J. Deep and wide digging for binding motifs in ChIP-seq data. Bioinformatics 26, 2622–2623 (2010).
Kuttippurathu, L. et al. CompleteMOTIFs: DNA motif discovery platform for transcription factor binding experiments. Bioinformatics 27, 715–717 (2011).
Jin, V.X., Apostolos, J., Nagisetty, N.S. & Farnham, P.J. W-ChIPMotifs: a web application tool for de novo motif discovery from ChIP-based high-throughput data. Bioinformatics 25, 3191–3193 (2009).
Zambelli, F., Pesole, G. & Pavesi, G. PscanChIP: finding over-represented transcription factor-binding site motifs and their correlations in sequences from ChIP-seq experiments. Nucleic Acids Res. 41, W535–W543 (2013).
Thomas-Chollier, M. et al. A complete workflow for the analysis of full-size ChIP-seq (and similar) data sets using peak-motifs. Nat. Protoc. 7, 1551–1568 (2012).
Sun, W. et al. TherMos: estimating protein-DNA binding energies from in vivo binding profiles. Nucleic Acids Res. 41, 5555–5568 (2013).
Bailey, T.L. et al. Practical guidelines for the comprehensive analysis of ChIP-seq data. PLoS Comput. Biol. 9, e1003326 (2013).
Stephen, G. et al. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res. 22, 1813–1831 (2012).
Park, P.J. ChIP-seq: advantages and challenges of a maturing technology. Nat. Rev. Genet. 10, 669–680 (2009).
Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
Sandelin, A., Alkema, W., Engstrom, P., Wasserman, W. & Lenhard, B. JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucliec Acids Res. 32, D91–D94 (2004).
Newburger, D.E. & Bulyk, M.L. UniPROBE: an online database of protein binding microarray data on protein-DNA interactions. Nucleic Acids Res. 37 (suppl. 1), D77–D82 (2009).
Gerber, A.P., Herschlag, D. & Brown, P.O. Extensive association of functionally and cytotopically related mRNAs with Puf family RNA-binding proteins in yeast. PLoS Biol. 2, e79 (2004).
Saint-Georges, Y. et al. Yeast mitochondrial biogenesis: a role for the PUF RNA-binding protein Puf3p in mRNA localization. PLoS ONE 3 e2293 (2008).
Ray, D. et al. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499, 172–177 (2013).
Kent, W.J. et al. The Human Genome Browser at UCSC. Genome Res. 12, 996–1006 (2002).
Goecks, J., Nekrutenko, A. & Taylor, J. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol. 11, R86 (2010).
Wadman, I.A. et al. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. EMBO J. 16, 3145–3157 (1997).
Whitington, T., Frith, M.C., Johnson, J. & Bailey, T.L. Inferring transcription factor complexes from ChIP-seq data. Nucleic Acids Res. 39, e98 (2011).
Hess, J., Angel, P. & Schorpp-Kistner, M. AP-1 subunits: quarrel and harmony among siblings. J. Cell Sci. 117, 5965–5973 (2004).
Tallack, M.R. et al. A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells. Genome Res. 20, 1052–1063 (2010).
Hogan, D.J., Riordan, D.P., Gerber, A.P., Herschlag, D. & Brown, P.O. Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system. PLoS Biol. 6, e255 (2008).
Sharov, A.A. & Ko, M.S.H. Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res. 16, 261–273 (2009).
Luehr, S., Hartmann, H. & Söding, J. The XXmotif web server for eXhaustive, weight matriX-based motif discovery in nucleotide sequences. Nucleic Acids Res. 40 (Web server issue): W104–W109 (2012).
Sung Rhee, H. & Franklin Pugh, B. Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide resolution. Cell 147, 1408–1419 (2011).
van Steensel, B. & Henikoff, S. Identification of in vivo DNA targets of chromatin proteins using tethered dam methyltransferase. Nat. Biotechnol. 18, 424–428 (2000).
Jolma, A. et al. DNA-binding specificities of human transcription factors. Cell 152, 327–339 (2013).
Licatalosi, D.D. et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464–469 (2008).
Sanford, J.R. et al. Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res. 19, 381–394 (2009).
Chi, S.W., Zang, J.B., Mele, A. & Darnell, R.B. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460, 479–486 (2009).
Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129–141 (2010).
König, J. et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17, 909–915 (2010).
Zhang, C. & Darnell, R.B. Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nat. Biotechnol. 29, 607–614 (2011).
Crawford, G.E. et al. Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res. 16, 123–131 (2006).
Giresi, P.G., Kim, J., McDaniell, R.M., Iyer, V.R. & Lieb, J.D. FAIRE (formaldehyde-assisted isolation of regulatory elements) isolates active regulatory elements from human chromatin. Genome Res. 17, 877–885 (2007).
Auerbach, R.K. et al. Mapping accessible chromatin regions using Sono-seq. Proc. Natl. Acad. Sci. USA 106, 14926–14931 (2009).
Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L. & Wold, B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat. Methods 5, 621–628 (2008).
Jin, F. et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503, 290–294 (2013).
Gupta, S., Stamatoyannopoulos, J.A., Bailey, T.L. & Noble, W.S. Quantifying similarity between motifs. Genome Biol. 8, R24 (2007).
Kishore, S. et al. A quantitative analysis of CLIP methods for identifying binding sites of RNA-binding proteins. Nat. Methods 8, 559–564 (2011).
Corcoran, D.L. et al. PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence data. Genome Biol. 12, R79 (2011).
Acknowledgements
This work was supported by the US National Institutes of Health awards R01 RR021692, R01 GM103544 and R01 GM098039.
Author information
Authors and Affiliations
Contributions
W.M. and W.S.N. wrote the initial draft. T.L.B. conceived the study cases, wrote the anticipated results section and wrote the second draft. W.M. and T.L.B. verified the study cases. W.S.N., W.M. and T.L.B. edited the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Ma, W., Noble, W. & Bailey, T. Motif-based analysis of large nucleotide data sets using MEME-ChIP. Nat Protoc 9, 1428–1450 (2014). https://doi.org/10.1038/nprot.2014.083
Published:
Issue Date:
DOI: https://doi.org/10.1038/nprot.2014.083
This article is cited by
-
Nuclear-localized CTEN is a novel transcriptional regulator and promotes cancer cell migration through its downstream target CDC27
Journal of Physiology and Biochemistry (2023)
-
N4-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana
Genome Biology (2022)
-
PIF4 enhances DNA binding of CDF2 to co-regulate target gene expression and promote Arabidopsis hypocotyl cell elongation
Nature Plants (2022)
-
FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis
Nature Communications (2022)
-
Alcohol induced increases in sperm Histone H3 lysine 4 trimethylation correlate with increased placental CTCF occupancy and altered developmental programming
Scientific Reports (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.