Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620266
Title:
Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.
Authors:
Jeffries, Aaron Richard; Uwanogho, D.A.; Cocks, G.; Perfect, L.W.; Dempster, Emma; Mill, Jonathan; Price, J.
Abstract:
Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter.
Citation:
Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming. 2016, 22 (10):1620-30 RNA
Publisher:
Highwire
Journal:
RNA (New York, N.Y.)
Issue Date:
Oct-2016
URI:
http://hdl.handle.net/11287/620266
DOI:
10.1261/rna.058347.116
PubMed ID:
27539784
Additional Links:
http://rnajournal.cshlp.org/content/22/10/1620.long
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1469-9001
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJeffries, Aaron Richarden
dc.contributor.authorUwanogho, D.A.en
dc.contributor.authorCocks, G.en
dc.contributor.authorPerfect, L.W.en
dc.contributor.authorDempster, Emmaen
dc.contributor.authorMill, Jonathanen
dc.contributor.authorPrice, J.en
dc.date.accessioned2017-03-10T16:04:40Z-
dc.date.available2017-03-10T16:04:40Z-
dc.date.issued2016-10-
dc.identifier.citationErasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming. 2016, 22 (10):1620-30 RNAen
dc.identifier.issn1469-9001-
dc.identifier.pmid27539784-
dc.identifier.doi10.1261/rna.058347.116-
dc.identifier.urihttp://hdl.handle.net/11287/620266-
dc.description.abstractClonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter.en
dc.language.isoenen
dc.publisherHighwireen
dc.relation.urlhttp://rnajournal.cshlp.org/content/22/10/1620.longen
dc.rightsArchived with thanks to RNA (New York, N.Y.)en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleErasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.en
dc.typeJournal Articleen
dc.identifier.journalRNA (New York, N.Y.)en
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.en
dc.description.fundingMR/K013807/1/Medical Research Council/United Kingdomen
dc.type.versionPublisheden

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