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Epigenetics
06 02, 2016;11 (6): 426-37.

Nucleosome positioning changes during human embryonic stem cell differentiation.

Wenjuan Zhang, Yaping Li, Michael Kulik, Rochelle L Tiedemann, Keith D Robertson, Stephen Dalton, Shaying Zhao
Author Information
  1. Wenjuan Zhang: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
  2. Yaping Li: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
  3. Michael Kulik: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
  4. Rochelle L Tiedemann: b Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
  5. Keith D Robertson: b Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
  6. Stephen Dalton: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
  7. Shaying Zhao: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
PMID: 27088311 DOI: 10.1080/15592294.2016.1176649

Abstract

Nucleosomes are the basic unit of chromatin. Nucleosome positioning (NP) plays a key role in transcriptional regulation and other biological processes. To better understand NP we used MNase-seq to investigate changes that occur as human embryonic stem cells (hESCs) transition to nascent mesoderm and then to smooth muscle cells (SMCs). Compared to differentiated cell derivatives, nucleosome occupancy at promoters and other notable genic sites, such as exon/intron junctions and adjacent regions, in hESCs shows a stronger correlation with transcript abundance and is less influenced by sequence content. Upon hESC differentiation, genes being silenced, but not genes being activated, display a substantial change in nucleosome occupancy at their promoters. Genome-wide, we detected a shift of NP to regions of higher G+C content as hESCs differentiate to SMCs. Notably, genomic regions with higher nucleosome occupancy harbor twice as many G↔C changes but fewer than half A↔T changes, compared to regions with lower nucleosome occupancy. Finally, our analysis indicates that the hESC genome is not rearranged and has a sequence mutation rate resembling normal human genomes. Our study reveals another unique feature of hESC chromatin, and sheds light on the relationship between nucleosome occupancy and sequence G+C content.

Keywords

G+C content MNase-seq hESC differentiation nucleosome occupancy nucleosome positioning sequence mutation transcription

References

  1. Bioinformatics. 2009 Jul 15;25(14):1754-60 [PMID: 19451168]
  2. Nat Commun. 2014 Aug 27;5:4719 [PMID: 25158628]
  3. Genome Res. 2010 Sep;20(9):1297-303 [PMID: 20644199]
  4. PLoS Genet. 2015 Jun 01;11(6):e1005277 [PMID: 26030765]
  5. Nature. 2007 Aug 2;448(7153):553-60 [PMID: 17603471]
  6. Cell Res. 2011 Sep;21(9):1332-42 [PMID: 21747414]
  7. Nature. 2011 Feb 10;470(7333):279-83 [PMID: 21160473]
  8. Mol Cell. 2010 May 28;38(4):603-13 [PMID: 20513434]
  9. BMC Bioinformatics. 2009 Dec 22;10:442 [PMID: 20028554]
  10. Genome Res. 2010 Mar;20(3):341-50 [PMID: 20086242]
  11. Genes Dev. 2011 Apr 1;25(7):679-84 [PMID: 21460036]
  12. Crit Rev Biochem Mol Biol. 2009 Jun;44(2-3):117-41 [PMID: 19514890]
  13. BMC Genomics. 2013 Apr 26;14:284 [PMID: 23622142]
  14. Nat Struct Mol Biol. 2013 Mar;20(3):267-73 [PMID: 23463311]
  15. Nat Protoc. 2009;4(1):44-57 [PMID: 19131956]
  16. Cell. 2011 Dec 23;147(7):1473-83 [PMID: 22196725]
  17. Genome Res. 2010 Mar;20(3):320-31 [PMID: 20133333]
  18. Stem Cell Res. 2012 Mar;8(2):154-64 [PMID: 22265736]
  19. Genome Biol Evol. 2015 Mar 18;7(4):1033-8 [PMID: 25786433]
  20. Science. 1998 Nov 6;282(5391):1145-7 [PMID: 9804556]
  21. Cell Stem Cell. 2013 Feb 7;12(2):180-92 [PMID: 23260488]
  22. Nat Protoc. 2013 Jan;8(1):203-12 [PMID: 23288320]
  23. Nat Genet. 2005 Oct;37(10):1099-103 [PMID: 16142235]
  24. Cell. 2013 Nov 7;155(4):934-47 [PMID: 24119843]
  25. Science. 2014 Dec 5;346(6214):1238-42 [PMID: 25477464]
  26. Cell. 2011 Dec 23;147(7):1484-97 [PMID: 22196726]
  27. Cell Tissue Res. 2014 Jun;356(3):457-66 [PMID: 24781148]
  28. Cell. 2006 Apr 21;125(2):315-26 [PMID: 16630819]
  29. Nucleic Acids Res. 2013 Aug;41(15):7302-12 [PMID: 23757189]
  30. DNA Res. 2009 Feb;16(1):45-58 [PMID: 19001483]
  31. Behav Brain Res. 2001 Nov 1;125(1-2):279-84 [PMID: 11682119]
  32. Mutat Res. 2008 Dec 1;647(1-2):30-8 [PMID: 18778722]
  33. Dev Growth Differ. 2010 Aug;52(6):483-91 [PMID: 20608951]
  34. Nature. 2012 Sep 6;489(7414):57-74 [PMID: 22955616]
  35. Cell Stem Cell. 2014 Jun 5;14(6):710-9 [PMID: 24905162]
  36. Nature. 2008 Nov 6;456(7218):60-5 [PMID: 18987735]
  37. Genome Res. 2011 Nov;21(11):1777-87 [PMID: 21903742]
  38. Nat Struct Mol Biol. 2012 Nov;19(11):1185-92 [PMID: 23085715]
  39. Nature. 2009 Nov 19;462(7271):315-22 [PMID: 19829295]
  40. Nature. 2012 Sep 6;489(7414):75-82 [PMID: 22955617]
  41. Semin Cell Dev Biol. 2003 Dec;14(6):359-67 [PMID: 15015743]
  42. Cell Stem Cell. 2007 Sep 13;1(3):286-98 [PMID: 18371363]
  43. Cancer Res. 2014 Sep 15;74(18):5045-56 [PMID: 25082814]
  44. Cell. 2008 Mar 7;132(5):887-98 [PMID: 18329373]
  45. Nature. 2003 May 8;423(6936):145-50 [PMID: 12736678]
  46. PLoS One. 2013 Apr 17;8(4):e62135 [PMID: 23614026]
  47. J Mol Biol. 2012 Mar 30;417(3):152-64 [PMID: 22310051]
  48. Nature. 2011 May 22;474(7352):516-20 [PMID: 21602827]
  49. Nature. 2013 Aug 22;500(7463):415-21 [PMID: 23945592]
  50. Nature. 2008 Nov 6;456(7218):66-72 [PMID: 18987736]
  51. Nature. 2010 Jul 15;466(7304):388-92 [PMID: 20512117]
  52. Cell. 2012 Jun 8;149(6):1381-92 [PMID: 22682255]
  53. Genome Res. 2016 Mar;26(3):351-64 [PMID: 26772197]
  54. Nature. 1997 Sep 18;389(6648):251-60 [PMID: 9305837]
  55. Nature. 2009 Mar 19;458(7236):362-6 [PMID: 19092803]
  56. Cell Stem Cell. 2011 Feb 4;8(2):200-13 [PMID: 21295276]
  57. PLoS Genet. 2012;8(11):e1003036 [PMID: 23166509]
  58. Bioinformatics. 2009 Aug 15;25(16):2078-9 [PMID: 19505943]
  59. Genome Res. 2014 Aug;24(8):1285-95 [PMID: 24812327]
  60. Stat Appl Genet Mol Biol. 2004;3:Article3 [PMID: 16646809]
  61. Nat Biotechnol. 2011 Nov 27;29(12):1132-44 [PMID: 22119741]
  62. Nat Biotechnol. 2007 Feb;25(2):244-8 [PMID: 17220878]
  63. Cell Stem Cell. 2009 Jan 9;4(1):80-93 [PMID: 19128795]
  64. Nat Rev Genet. 2009 Mar;10(3):161-72 [PMID: 19204718]
  65. Nature. 2011 May 19;473(7347):398-402 [PMID: 21460836]
  66. Epigenetics. 2009 Feb 16;4(2):93-7 [PMID: 19242104]
  67. Nature. 2015 Feb 19;518(7539):331-6 [PMID: 25693564]
  68. Nature. 2006 Aug 17;442(7104):772-8 [PMID: 16862119]
  69. Cell Rep. 2015 Oct 6;13(1):61-69 [PMID: 26411677]

Grants

  1. R01 CA182093/NCI NIH HHS

MeSH Term

Base Composition
Cell Differentiation
Cell Line
Chromatin Assembly and Disassembly
Embryonic Stem Cells
Gene Expression Regulation, Developmental
Humans
Myocytes, Smooth Muscle
Nucleosomes
Promoter Regions, Genetic

Chemicals

Nucleosomes
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 9

Word Cloud

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