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Resolving the Genomic Localization of the Kollerin Cohesin-Loader Complex

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Cohesin and Condensin

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1515))

Abstract

The kollerin complex, consisting of Scc2/Scc4 in yeast and Nipbl/Mau2 in vertebrates, is crucial for the chromatin-association of the cohesin complex and therefore for the critical functions of cohesin in cell division, transcriptional regulation and chromatin organisation. Despite the recent efforts to determine the genomic localization of the kollerin complex in different cell lines, major questions still remain unresolved, for instance where cohesin is actually loaded onto chromatin. Further, Nipbl seems to have also additional roles, for instance as transcription factor.

This chapter summarizes our current knowledge on kollerin function and the recent studies on the genomic localization of Scc2, highlighting and critically discussing controversial data.

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References

  1. Dorsett D (2004) Adherin: key to the cohesin ring and Cornelia de Lange syndrome. Curr Biol 14(19):R834–R836

    Article  CAS  PubMed  Google Scholar 

  2. Nasmyth K (2011) Cohesin: a catenase with separate entry and exit gates? Nat Cell Biol 13(10):1170–1177

    Article  CAS  PubMed  Google Scholar 

  3. Dorsett D (2007) Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes. Chromosoma 116(1):1–13

    Article  PubMed  Google Scholar 

  4. Wendt KS et al (2008) Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451(7180):796–801

    Article  CAS  PubMed  Google Scholar 

  5. Zuin J et al (2014) A cohesin-independent role for NIPBL at promoters provides insights in CdLS. PLoS Genet 10(2), e1004153

    Article  PubMed  PubMed Central  Google Scholar 

  6. Muto A et al (2011) Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biol 9(10), e1001181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rollins RA et al (2004) Drosophila nipped-B protein supports sister chromatid cohesion and opposes the stromalin/Scc3 cohesion factor to facilitate long-range activation of the cut gene. Mol Cell Biol 24(8):3100–3111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ivanov D, Nasmyth K (2005) A topological interaction between cohesin rings and a circular minichromosome. Cell 122(6):849–860

    Article  CAS  PubMed  Google Scholar 

  9. Gligoris TG et al (2014) Closing the cohesin ring: structure and function of its Smc3-kleisin interface. Science 346(6212):963–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Miller MP, Amon A, Unal E (2013) Meiosis I: when chromosomes undergo extreme makeover. Curr Opin Cell Biol 25(6):687–696

    Article  CAS  PubMed  Google Scholar 

  11. Dixon JR et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zuin J et al (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci U S A 111(3):996–1001

    Article  CAS  PubMed  Google Scholar 

  13. Seitan V et al (2013) Cohesin-based chromatin interactions enable regulated gene expression within pre-existing architectural compartments. Genome Res 23(12):2066–2077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sofueva S et al (2013) Cohesin-mediated interactions organize chromosomal domain architecture. EMBO J 32(24):3119–3129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wendt KS, Grosveld FG (2014) Transcription in the context of the 3D nucleus. Curr Opin Genet Dev 25C:62–67

    Article  Google Scholar 

  16. Watrin E, Peters JM (2006) Cohesin and DNA damage repair. Exp Cell Res 312(14):2687–2693

    Article  CAS  PubMed  Google Scholar 

  17. Ciosk R et al (2000) Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins. Mol Cell 5(2):243–254

    Article  CAS  PubMed  Google Scholar 

  18. Gillespie PJ, Hirano T (2004) Scc2 couples replication licensing to sister chromatid cohesion in Xenopus egg extracts. Curr Biol 14(17):1598–1603

    Article  CAS  PubMed  Google Scholar 

  19. Lengronne A et al (2004) Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 430(6999):573–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Watrin E et al (2006) Human Scc4 is required for cohesin binding to chromatin, sister-chromatid cohesion, and mitotic progression. Curr Biol 16(9):863–874

    Article  CAS  PubMed  Google Scholar 

  21. Arumugam P et al (2003) ATP hydrolysis is required for cohesin's association with chromosomes. Curr Biol 13(22):1941–1953

    Article  CAS  PubMed  Google Scholar 

  22. Kogut I et al (2009) The Scc2/Scc4 cohesin loader determines the distribution of cohesin on budding yeast chromosomes. Genes Dev 23(19):2345–2357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hu B et al (2011) ATP hydrolysis is required for relocating cohesin from sites occupied by its Scc2/4 loading complex. Curr Biol 21(1):12–24

    Article  CAS  PubMed  Google Scholar 

  24. Schmidt CK, Brookes N, Uhlmann F (2009) Conserved features of cohesin binding along fission yeast chromosomes. Genome Biol 10(5):R52

    Article  PubMed  PubMed Central  Google Scholar 

  25. Eckert CA, Gravdahl DJ, Megee PC (2007) The enhancement of pericentromeric cohesin association by conserved kinetochore components promotes high-fidelity chromosome segregation and is sensitive to microtubule-based tension. Genes Dev 21(3):278–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ng TM et al (2009) Pericentromeric sister chromatid cohesion promotes kinetochore biorientation. Mol Biol Cell 20(17):3818–3827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fernius J, Marston AL (2009) Establishment of cohesion at the pericentromere by the Ctf19 kinetochore subcomplex and the replication fork-associated factor, Csm3. PLoS Genet 5(9), e1000629

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fernius J et al (2013) Cohesin-dependent association of scc2/4 with the centromere initiates pericentromeric cohesion establishment. Curr Biol 23(7):599–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. D'Ambrosio C et al (2008) Identification of cis-acting sites for condensin loading onto budding yeast chromosomes. Genes Dev 22(16):2215–2227

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lengronne A et al (2006) Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. Mol Cell 23(6):787–799

    Article  CAS  PubMed  Google Scholar 

  31. Lopez-Serra L et al (2013) Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation. Curr Biol 23(1):64–69

    Article  CAS  PubMed  Google Scholar 

  32. Hinshaw SM et al (2015) Structural evidence for Scc4-dependent localization of cohesin loading. Elife 4, e06057

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chao WC et al (2015) Structural studies reveal the functional modularity of the Scc2-Scc4 Cohesin loader. Cell Rep 12(5):719–725

    Article  CAS  PubMed  Google Scholar 

  34. Braunholz D et al (2012) Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction. Eur J Hum Genet 20(3):271–276

    Article  CAS  PubMed  Google Scholar 

  35. Murayama Y, Uhlmann F (2014) Biochemical reconstitution of topological DNA binding by the cohesin ring. Nature 505(7483):367–371

    Article  CAS  PubMed  Google Scholar 

  36. Misulovin Z et al (2008) Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome. Chromosoma 117(1):89–102

    Article  CAS  PubMed  Google Scholar 

  37. MacAlpine HK et al (2010) Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading. Genome Res 20(2):201–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Takahashi TS et al (2008) Cdc7-Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts. Genes Dev 22(14):1894–1905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bermudez VP et al (2012) In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader complex. Proc Natl Acad Sci U S A 109(24):9366–9371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li Y et al (2013) Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes. BMC Genomics 14:553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schmidt D et al (2010) A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res 20(5):578–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kagey MH et al (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467(7314):430–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Estaras C, Benner C, Jones KA (2015) SMADs and YAP compete to control elongation of beta-catenin:LEF-1-recruited RNAPII during hESC differentiation. Mol Cell 58(5):780–793

    Article  CAS  PubMed  Google Scholar 

  44. Euskirchen GM et al (2007) Mapping of transcription factor binding regions in mammalian cells by ChIP: comparison of array- and sequencing-based technologies. Genome Res 17(6):898–909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rozowsky J et al (2009) PeakSeq enables systematic scoring of ChIP-seq experiments relative to controls. Nat Biotechnol 27(1):66–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dowen JM et al (2013) Multiple structural maintenance of chromosome complexes at transcriptional regulatory elements. Stem Cell Rep 1(5):371–378

    Article  CAS  Google Scholar 

  47. Furuya K, Takahashi K, Yanagida M (1998) Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase. Genes Dev 12(21):3408–3418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Woodman J et al (2014) Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity. Proc Natl Acad Sci U S A 111(19):7060–7065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Strom L et al (2004) Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair. Mol Cell 16(6):1003–1015

    Article  PubMed  Google Scholar 

  50. Watrin E, Peters JM (2009) The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells. EMBO J 28(17):2625–2635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Oka Y et al (2011) Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1gamma in human cells. Biochem Biophys Res Commun 411(4):762–767

    Article  CAS  PubMed  Google Scholar 

  52. Chien R et al (2011) Cohesin mediates chromatin interactions that regulate mammalian beta-globin expression. J Biol Chem 286(20):17870–17878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Muto A et al (2014) Nipbl and mediator cooperatively regulate gene expression to control limb development. PLoS Genet 10(9), e1004671

    Article  PubMed  PubMed Central  Google Scholar 

  54. Nolen LD et al (2013) Regional chromatin decompaction in Cornelia de Lange syndrome associated with NIPBL disruption can be uncoupled from cohesin and CTCF. Hum Mol Genet 22(20):4180–4193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I thank Erwan Watrin from the Universite´ de Rennes/France for input and critical comments on the chapter.

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Correspondence to Kerstin S. Wendt .

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Wendt, K.S. (2017). Resolving the Genomic Localization of the Kollerin Cohesin-Loader Complex. In: Yokomori, K., Shirahige, K. (eds) Cohesin and Condensin. Methods in Molecular Biology, vol 1515. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6545-8_7

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  • DOI: https://doi.org/10.1007/978-1-4939-6545-8_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6543-4

  • Online ISBN: 978-1-4939-6545-8

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