Genome-Wide Occupancy Analysis by ChIP-chip and ChIP-Seq

  • Hong HaoEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


Interaction between protein complexes and the genome mediates essential functions including gene regulation, genome integrity, and chromatin organization. Recent advances in chromatin immunoprecipitaion (ChIP)-chip and ChIP-Seq technologies have enabled genome-wide identification of occupancy of transcription factors and modified histones that is critical for uncovering gene regulatory networks. This review discusses ChIP-chip and ChIP-Seq technology, their pitfalls, insights from genome-wide occupancy studies, and applications pertaining to vertebrate retina.


ChIP-chip ChIP-Seq Chromatin signature Transcription Enhancer Histone Transcription regulatory network Photoreceptor Development 



I am grateful to Dr. Anand Swaroop for advice. This work was supported by intramural funds of the National Eye Institute.


  1. Akimoto M, Cheng H, Zhu D et al (2006) Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proc Natl Acad Sci USA 103:3890  –3895PubMedCrossRefGoogle Scholar
  2. Barski A, Zhao K (2009) Genomic location analysis by ChIP-seq. J Cell Biochem 107:11–18PubMedCrossRefGoogle Scholar
  3. Bienvenu F, Jirawatnotai S, Elias JE et al (2010) Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature 463:374  –378PubMedCrossRefGoogle Scholar
  4. Chen X et al (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106  –1117PubMedCrossRefGoogle Scholar
  5. Corbo JC, Lawrence KA, Karlstetter M et al (2010) CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors. Genome Res 20:1512–1525PubMedCrossRefGoogle Scholar
  6. Farnham PJ (2009) Insights from genomic profiling of transcription factors. Nat Rev Genet 10:605–616PubMedCrossRefGoogle Scholar
  7. Heintzman ND, Ren B (2007) The gateway to transcription: identifying, characterizing and understanding promoters in the eukaryotic genome. Cell Mol Life Sci 64:386  –  400PubMedCrossRefGoogle Scholar
  8. Heintzman ND, Stuart RK, Hon G et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318PubMedCrossRefGoogle Scholar
  9. Heintzman ND et al (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459:108–112PubMedCrossRefGoogle Scholar
  10. Hon GC, Hawkins RD, Ren B (2009) Predictive chromatin signatures in the mammalian genome. Hum Mol Genet 18:R195–201PubMedCrossRefGoogle Scholar
  11. Kim TH, Ren B (2006) Genome-wide analysis of protein-DNA interactions. Annu Rev Genomics Hum Genet 7:81–102PubMedCrossRefGoogle Scholar
  12. Kirmizis A, Farnham PJ (2004) Genomic approaches that aid in the identification of transcription factor target genes. Exp Biol Med (Maywood) 229:705–721Google Scholar
  13. Lemon B, Tjian R (2000) Orchestrated response: a symphony of transcription factors for gene control. Genes Dev 14:2551–2569PubMedCrossRefGoogle Scholar
  14. Livesey FJ, Cepko CL (2001) Vertebrate neural cell-fate determination: lessons from the retina. Nat Rev Neurosci 2:109  –118PubMedCrossRefGoogle Scholar
  15. Marquardt T, Gruss P (2002) Generating neuronal diversity in the retina: one for nearly all. Trends Neurosci 25:32–38PubMedCrossRefGoogle Scholar
  16. Maston GA, Evans SK, Green MR (2006) Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet 7:29  –59PubMedCrossRefGoogle Scholar
  17. Miele A, Dekker J (2008) Long-range chromosomal interactions and gene regulation. Mol Biosyst 4:1046  –1057PubMedCrossRefGoogle Scholar
  18. Mikkelsen TS et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553  –560PubMedCrossRefGoogle Scholar
  19. Park PJ (2009) ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10:669–  680PubMedCrossRefGoogle Scholar
  20. Ren B, Cam H, Takahashi Y et al (2002) E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev 16:245–256PubMedCrossRefGoogle Scholar
  21. Ren B, Robert F, Wyrick JJ et al (2000) Genome-wide location and function of DNA binding proteins. Science 290:2306  –2309PubMedCrossRefGoogle Scholar
  22. Simonis M, Kooren J, de Laat W (2007) An evaluation of 3C-based methods to capture DNA interactions. Nat Methods 4:895–901PubMedCrossRefGoogle Scholar
  23. Swaroop A, Kim D, Forrest D (2010) Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci 11:563–576PubMedCrossRefGoogle Scholar
  24. Tummala P, Mali RS, Guzman E, Zhang X, Mitton KP (2010) Temporal ChIP-on-Chip of RNA-Polymerase-II to detect novel gene activation events during photoreceptor maturation. Mol Vis 16:252–271PubMedGoogle Scholar
  25. Weinmann AS, Yan PS, Oberley MJ, Huang TH, Farnham PJ (2002) Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes Dev 16:235–244PubMedCrossRefGoogle Scholar
  26. Wright AF, Chakarova CF, Abd El-Aziz MM, Bhattacharya SS (2010) Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet 11:273–284PubMedCrossRefGoogle Scholar
  27. Zecchini V, Mills IG (2009) Putting chromatin immunoprecipitation into context. J Cell Biochem 107:19  –29PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Neurobiology-Neurodegeneration and Repair LaboratoryNational Eye Institute, National Institutes of HealthBethesdaUSA

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