Abstract
Chromatin states are the key to embryonic stem cell pluripotency and differentiation. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-Seq) is increasingly used to map chromatin states and to functionally annotate the genome. Many ChIP-Seq profiles, especially those of histone methylations, are noisy and diffuse. Here we describe SICER (Zang et al., Bioinformatics 25(15):1952–1958, 2009), an algorithm specifically designed to identify disperse ChIP-enriched regions with high sensitivity and specificity. This algorithm has found a lot of applications in epigenomic studies. In this Chapter, we will demonstrate in detail how to run SICER to delineate ChIP-enriched regions and assess their statistical significance, and to identify regions of differential enrichment when two chromatin states are compared.
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References
Barski A, Cuddapah S, Cui KR, Roh TY, Schones DE, Wang ZB, Wei G, Chepelev I, Zhao KJ (2007) High-resolution profiling of histone methylations in the human genome. Cell 129(4):823–837
Wang ZB, Zang CZ, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui KR, Roh TY, Peng WQ, Zhang MQ, Zhao KJ (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40(7):897–903
Wang Z, Zang C, Cui K, Schones DE, Barski A, Peng W, Zhao K (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138(5):1019–1031
Zang C, Schones DE, Zeng C, Cui K, Zhao K, Peng W (2009) A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25(15):1952–1958
Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T (1999) Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. EMBO J 18(7):1923–1938
Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410(6824):120–124
Lachner M, O’Carroll N, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410(6824):116–120
Schwartz YB, Pirrotta V (2007) Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev Genet 8(1):9–22
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B 57:289–300
Shimazaki H, Shinomoto S (2007) A method for selecting the bin size of a time histogram. Neural Comput 19:1503–1527
Song Q, Smith AD (2011) Identifying dispersed epigenomic domains from ChIP-Seq data. Bioinformatics 27(6):870–871. doi:10.1093/bioinformatics/btr030
Koehler R, Issac H, Cloonan N, Grimmond SM (2010) The uniqueome: a mappability resource for short-tag sequencing. Bioinformatics. doi:10.1093/bioinformatics/btq640
Quinlan AR, Hall IM (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26(6):841–842. doi:10.1093/bioinformatics/btq033
The EPC (2011) A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9(4):e1001046. doi:10.1371/journal.pbio.1001046
Rosenbloom KR, Sloan CA, Malladi VS, Dreszer TR, Learned K, Kirkup VM, Wong MC, Maddren M, Fang R, Heitner SG, Lee BT, Barber GP, Harte RA, Diekhans M, Long JC, Wilder SP, Zweig AS, Karolchik D, Kuhn RM, Haussler D, Kent WJ (2012) ENCODE data in the UCSC Genome Browser: year 5 update. Nucleic Acids Res. doi:10.1093/nar/gks1172
Wang L, Xu S, Lee J-E, Baldridge A, Grullon S, Peng W, Ge K (2013) Histone H3K9 methyltransferase G9a represses PPAR[gamma] expression and adipogenesis. EMBO J 32(1):45–59. http://www.nature.com/emboj/journal/v32/n1/suppinfo/emboj2012306a_S1.html
Acknowledgement
This work was supported in part by the Intramural Research Program of the NIDDK, NIH to KG.
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Xu, S., Grullon, S., Ge, K., Peng, W. (2014). Spatial Clustering for Identification of ChIP-Enriched Regions (SICER) to Map Regions of Histone Methylation Patterns in Embryonic Stem Cells. In: Kidder, B. (eds) Stem Cell Transcriptional Networks. Methods in Molecular Biology, vol 1150. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0512-6_5
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DOI: https://doi.org/10.1007/978-1-4939-0512-6_5
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