Nucleosome repositioning during differentiation of a human myeloid leukemia cell line
Date
2017-02-23Author
Teif, Vladimir B.
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Mallm, Jan-Philipp
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Sharma, Tanvi
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Mark Welch, David B.
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Rippe, Karsten
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Eils, Roland
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Langowski, Jörg
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Olins, Ada L.
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Olins, Donald E.
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https://hdl.handle.net/1912/8989As published
https://doi.org/10.1080/19491034.2017.1295201DOI
10.1080/19491034.2017.1295201Keyword
CTCF: Epichromatin; Histone modifications; Nucleosome positioning; Nucleosome repeat length; Transcription factor bindingAbstract
Cell differentiation is associated with changes in chromatin organization and gene expression. In
this study, we examine chromatin structure following differentiation of the human myeloid
leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with
phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes
in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and
properties of epichromatin (surface chromatin adjacent to the nuclear envelope). Nucleosome
positions changed genome-wide, exhibiting a specific class of alterations involving nucleosome loss
in extended (»1kb) regions, pronounced in enhancers and promoters. Genes that lost nucleosomes
at their promoters showed a tendency to be upregulated. On the other hand, nucleosome gain did
not show simple effects on transcript levels. The average genome-wide nucleosome repeat length
(NRL) did not change significantly with differentiation. However, we detected an approximate 10 bp
NRL decrease around the haematopoietic transcription factor (TF) PU.1 and the architectural protein
CTCF, suggesting an effect on NRL proximal to TF binding sites. Nucleosome occupancy changed in
regions associated with active promoters in differentiated cells, compared with untreated HL-60/S4
cells. Epichromatin regions revealed an increased GC content and high nucleosome density
compared with surrounding chromatin. Epichromatin showed depletion of major histone
modifications and revealed enrichment with PML body-associated genes. In general, chromatin
changes during HL-60/S4 differentiation appeared to be more localized to regulatory regions,
compared with genome-wide changes among diverse cell types studied elsewhere.
Description
© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nucleus 8 (2017): 188-204, doi:10.1080/19491034.2017.1295201.
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