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Hox Genes pp 121-131 | Cite as

Mining the Cis-Regulatory Elements of Hox Clusters

  • Navneet Kaur Matharu
  • Rakesh K. MishraEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1196)

Abstract

Hox clusters have served as a favorite system to study the role of cis-regulatory elements at multiple layers of gene regulation. Organization and regulation of Hox genes show remarkable conservation and determine the anterior–posterior body axis across the bilaterians. Identification of a variety of regulatory regions within the complex and around it, embedded primarily in the noncoding part of the corresponding genomic region that can spread 100–150 kb, is a challenging problem. Multiple experimental and computational tools need to be employed to investigate functional features of such elements. Here we discuss parallel approaches to mine the most plausible regulatory information from the noncoding sequences of Hox clusters, among diverse species.

Key words

Hox cluster Cis-regulatory element (CRE) Polycomb response element (PRE) Insulator Chromatin domain boundary CNCS 

Notes

Acknowledgements

Authors acknowledge financial support from Council of Scientific and Industrial Research (CSIR) through network programs BSC0208 and BSC0118.

References

  1. 1.
    Nobrega MA, Ovcharenko I, Afzal V, Rubin EM (2003) Scanning human gene deserts for long-range enhancers. Science 302(5644):413PubMedCrossRefGoogle Scholar
  2. 2.
    Boffelli D, Nobrega MA, Rubin EM (2004) Comparative genomics at the vertebrate extremes. Nat Rev Genet 5(6):456–465PubMedCrossRefGoogle Scholar
  3. 3.
    Lee AP, Koh EG, Tay A, Brenner S, Venkatesh B (2006) Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters. Proc Natl Acad Sci U S A 103(18):6994–6999PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Martin DI et al (2011) Phyloepigenomic comparison of great apes reveals a correlation between somatic and germline methylation states. Genome Res 21(12):2049–2057PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Lai F et al (2013) Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494(7438):497–501PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Li W et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498(7455):516–520PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Hekimoglu B, Ringrose L (2009) Non-coding RNAs in polycomb/trithorax regulation. RNA Biol 6(2):129–137PubMedCrossRefGoogle Scholar
  8. 8.
    Thomas JW et al (2003) Comparative analyses of multi-species sequences from targeted genomic regions. Nature 424(6950):788–793PubMedCrossRefGoogle Scholar
  9. 9.
    Frasch M, Chen X, Lufkin T (1995) Evolutionary-conserved enhancers direct region-specific expression of the murine Hoxa-1 and Hoxa-2 loci in both mice and Drosophila. Development 121(4):957–974PubMedGoogle Scholar
  10. 10.
    Poulin F et al (2005) In vivo characterization of a vertebrate ultraconserved enhancer. Genomics 85(6):774–781PubMedCrossRefGoogle Scholar
  11. 11.
    Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE (2010) A region of the human HOXD cluster that confers polycomb-group responsiveness. Cell 140(1):99–110PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Wang QF et al (2007) Detection of weakly conserved ancestral mammalian regulatory sequences by primate comparisons. Genome Biol 8(1):R1PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Prabhakar S et al (2008) Human-specific gain of function in a developmental enhancer. Science 321(5894):1346–1350PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Sabarinadh C, Subramanian S, Tripathi A, Mishra RK (2004) Extreme conservation of noncoding DNA near HoxD complex of vertebrates. BMC Genomics 5:75PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Matharu NK, Hussain T, Sankaranarayanan R, Mishra RK (2010) Vertebrate homologue of Drosophila GAGA factor. J Mol Biol 400(3):434–447PubMedCrossRefGoogle Scholar
  16. 16.
    Vasanthi D, Anant M, Srivastava S, Mishra RK (2010) A functionally conserved boundary element from the mouse HoxD locus requires GAGA factor in Drosophila. Development 137(24):4239–4247PubMedCrossRefGoogle Scholar
  17. 17.
    Srinivasan A, Mishra RK (2012) Chromatin domain boundary element search tool for Drosophila. Nucleic Acids Res 40(10):4385–4395PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Ahanger SH, Srinivasan A, Vasanthi D, Shouche YS, Mishra RK (2013) Conserved boundary elements from the Hox complex of mosquito, Anopheles gambiae. Nucleic Acids Res 41(2):804–816PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469(7330):343–349PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Karolchik D et al (2013) The UCSC Genome Browser database: 2014 update. Nucleic Acids Res 42(Database issue):D764–D770PubMedCentralPubMedGoogle Scholar
  21. 21.
    Srivastava S, Puri D, Garapati HS, Dhawan J, Mishra RK (2013) Vertebrate GAGA factor associated insulator elements demarcate homeotic genes in the HOX clusters. Epigenetics Chromatin 6(1):8PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Centre for Cellular and Molecular BiologyCouncil of Scientific and Industrial ResearchHyderabadIndia

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