TY - JOUR
T1 - Nucleosome positioning changes during human embryonic stem cell differentiation
AU - Zhang, Wenjuan
AU - Li, Yaping
AU - Kulik, Michael
AU - Tiedemann, Rochelle L.
AU - Robertson, Keith D.
AU - Dalton, Stephen
AU - Zhao, Shaying
N1 - Publisher Copyright:
© 2016 Taylor & Francis Group, LLC.
PY - 2016/6/2
Y1 - 2016/6/2
N2 - 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.
AB - 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.
KW - G+C content
KW - MNase-seq
KW - hESC differentiation
KW - nucleosome occupancy
KW - nucleosome positioning
KW - sequence mutation
KW - transcription
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U2 - 10.1080/15592294.2016.1176649
DO - 10.1080/15592294.2016.1176649
M3 - Article
C2 - 27088311
AN - SCOPUS:84973176762
SN - 1559-2294
VL - 11
SP - 426
EP - 437
JO - Epigenetics
JF - Epigenetics
IS - 6
ER -