title: Nucleosome positioning changes during human embryonic stem cell differentiation.
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.
authors.affiliation: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kulik
authors.affiliation: b Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
authors.forename: Rochelle L
authors.initials: RL
authors.lastname: Tiedemann
authors.affiliation: b Department of Molecular Pharmacology and Experimental Therapeutics , Mayo Clinic , Rochester , MN , USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Robertson
authors.affiliation: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dalton
authors.affiliation: a Department of Biochemistry and Molecular Biology , Institute of Bioinformatics, University of Georgia , Athens , GA , USA.
authors.forename: Shaying
authors.initials: S
authors.lastname: Zhao
mesh_terms: D001482:Base Composition; D002454:Cell Differentiation; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D009707:Nucleosomes
keywords: G+C content; MNase-seq; hESC differentiation; nucleosome occupancy; nucleosome positioning; sequence mutation; transcription