Spatial Clustering for Identification of ChIP-Enriched Regions (SICER) to Map Regions of Histone Methylation Patterns in Embryonic Stem Cells
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.
Key wordsChIP-Seq Histone modifications Epigenetic modifications Epigenome SICER
This work was supported in part by the Intramural Research Program of the NIDDK, NIH to KG.
- 5.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):1923–1938PubMedCentralPubMedCrossRefGoogle Scholar
- 9.Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B 57:289–300Google Scholar
- 15.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 Google Scholar
- 16.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 Google Scholar