Nucleosome Dynamics of Human IPSC During Neural Differentiation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2019 May 1

PMID 31036712

Citations 3

Authors

Janet C Harwood

Nicholas A Kent

Nicholas D Allen

Adrian J Harwood

Affiliations

Soon will be listed here.

Abstract

Nucleosome positioning is important for neurodevelopment, and genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. To investigate changes in nucleosome positioning during neural differentiation, we generate genome-wide nucleosome maps from an undifferentiated human-induced pluripotent stem cell (hiPSC) line and after its differentiation to the neural progenitor cell (NPC) stage. We find that nearly 3% of nucleosomes are highly positioned in NPC, but significantly, there are eightfold fewer positioned nucleosomes in pluripotent cells, indicating increased positioning during cell differentiation. Positioned nucleosomes do not strongly correlate with active chromatin marks or gene transcription. Unexpectedly, we find a small population of nucleosomes that occupy similar positions in pluripotent and neural progenitor cells and are found at binding sites of the key gene regulators NRSF/REST and CTCF Remarkably, the presence of these nucleosomes appears to be independent of the associated regulatory complexes. Together, these results present a scenario in human cells, where positioned nucleosomes are sparse and dynamic, but may act to alter gene expression at a distance via the structural conformation at sites of chromatin regulation.

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References

Ong C, Corces V . CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet. 2014; 15(4):234-46. PMC: 4610363. DOI: 10.1038/nrg3663. View

Bhinge A, Poschmann J, Namboori S, Tian X, Loh S, Traczyk A . MiR-135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF-β/BMP signaling. EMBO J. 2014; 33(11):1271-83. PMC: 4198029. DOI: 10.1002/embj.201387215. View

Ishihara K, Oshimura M, Nakao M . CTCF-dependent chromatin insulator is linked to epigenetic remodeling. Mol Cell. 2006; 23(5):733-42. DOI: 10.1016/j.molcel.2006.08.008. View

Mueller B, Mieczkowski J, Kundu S, Wang P, Sadreyev R, Tolstorukov M . Widespread changes in nucleosome accessibility without changes in nucleosome occupancy during a rapid transcriptional induction. Genes Dev. 2017; 31(5):451-462. PMC: 5393060. DOI: 10.1101/gad.293118.116. View

Trynka G, Raychaudhuri S . Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases. Curr Opin Genet Dev. 2013; 23(6):635-41. PMC: 4073234. DOI: 10.1016/j.gde.2013.10.009. View

Narlikar G, Sundaramoorthy R, Owen-Hughes T . Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes. Cell. 2013; 154(3):490-503. PMC: 3781322. DOI: 10.1016/j.cell.2013.07.011. View

Kundaje A, Kyriazopoulou-Panagiotopoulou S, Libbrecht M, Smith C, Raha D, Winters E . Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory elements. Genome Res. 2012; 22(9):1735-47. PMC: 3431490. DOI: 10.1101/gr.136366.111. View

Bouazoune K, Kingston R . Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders. Proc Natl Acad Sci U S A. 2012; 109(47):19238-43. PMC: 3511097. DOI: 10.1073/pnas.1213825109. View

Carone B, Hung J, Hainer S, Chou M, Carone D, Weng Z . High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Dev Cell. 2014; 30(1):11-22. PMC: 4184102. DOI: 10.1016/j.devcel.2014.05.024. View

10.

Chambers S, Fasano C, Papapetrou E, Tomishima M, Sadelain M, Studer L . Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009; 27(3):275-80. PMC: 2756723. DOI: 10.1038/nbt.1529. View

11.

de Dieuleveult M, Yen K, Hmitou I, Depaux A, Boussouar F, Bou Dargham D . Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells. Nature. 2016; 530(7588):113-6. PMC: 4871117. DOI: 10.1038/nature16505. View

12.

McClelland S, Flynn C, Dube C, Richichi C, Zha Q, Ghestem A . Neuron-restrictive silencer factor-mediated hyperpolarization-activated cyclic nucleotide gated channelopathy in experimental temporal lobe epilepsy. Ann Neurol. 2011; 70(3):454-64. PMC: 3177145. DOI: 10.1002/ana.22479. View

13.

Reimold A, Grusby M, Kosaras B, FRIES J, Mori R, Maniwa S . Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature. 1996; 379(6562):262-5. DOI: 10.1038/379262a0. View

14.

Dekker J, Belmont A, Guttman M, Leshyk V, Lis J, Lomvardas S . The 4D nucleome project. Nature. 2017; 549(7671):219-226. PMC: 5617335. DOI: 10.1038/nature23884. View

15.

Lantermann A, Straub T, Stralfors A, Yuan G, Ekwall K, Korber P . Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae. Nat Struct Mol Biol. 2010; 17(2):251-7. DOI: 10.1038/nsmb.1741. View

16.

Langmead B, Trapnell C, Pop M, Salzberg S . Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009; 10(3):R25. PMC: 2690996. DOI: 10.1186/gb-2009-10-3-r25. View

17.

Kent N, Adams S, Moorhouse A, Paszkiewicz K . Chromatin particle spectrum analysis: a method for comparative chromatin structure analysis using paired-end mode next-generation DNA sequencing. Nucleic Acids Res. 2010; 39(5):e26. PMC: 3061068. DOI: 10.1093/nar/gkq1183. View

18.

Wu J, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S . Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proc Natl Acad Sci U S A. 2010; 107(11):5254-9. PMC: 2841935. DOI: 10.1073/pnas.0914114107. View

19.

Jiang C, Pugh B . A compiled and systematic reference map of nucleosome positions across the Saccharomyces cerevisiae genome. Genome Biol. 2009; 10(10):R109. PMC: 2784324. DOI: 10.1186/gb-2009-10-10-r109. View

20.

Platt J, Kent N, Kimmel A, Harwood A . Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in . Genome Res. 2017; 27(4):591-600. PMC: 5378177. DOI: 10.1101/gr.216309.116. View