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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)426-437
Number of pages12
JournalEpigenetics
Volume11
Issue number6
DOIs
StatePublished - Jun 2 2016

Fingerprint

Nucleosomes
Cell Differentiation
Base Composition
Chromatin
Smooth Muscle Myocytes
Genome
Biological Phenomena
Human Embryonic Stem Cells
Mesoderm
Human Genome
Mutation Rate
Introns
Genes
Exons

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Nucleosome positioning changes during human embryonic stem cell differentiation. / Zhang, Wenjuan; Li, Yaping; Kulik, Michael; Tiedemann, Rochelle L.; Robertson, Keith D; Dalton, Stephen; Zhao, Shaying.

In: Epigenetics, Vol. 11, No. 6, 02.06.2016, p. 426-437.

Research output: Contribution to journalArticle

Zhang, W, Li, Y, Kulik, M, Tiedemann, RL, Robertson, KD, Dalton, S & Zhao, S 2016, 'Nucleosome positioning changes during human embryonic stem cell differentiation', Epigenetics, vol. 11, no. 6, pp. 426-437. https://doi.org/10.1080/15592294.2016.1176649
Zhang, Wenjuan ; Li, Yaping ; Kulik, Michael ; Tiedemann, Rochelle L. ; Robertson, Keith D ; Dalton, Stephen ; Zhao, Shaying. / Nucleosome positioning changes during human embryonic stem cell differentiation. In: Epigenetics. 2016 ; Vol. 11, No. 6. pp. 426-437.
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