liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. (Centre for Individualised Medicine)
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Visa övriga samt affilieringar
2015 (Engelska)Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 16, s. 11-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BackgroundThe DNA methylation profile of mammalian cell lines differs from the primary tissue from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture. Few studies have directly examined the initial epigenetic and transcriptional consequences of adaptation of primary mammalian cells to culture, and the potential mechanisms through which this epigenetic dysregulation occurs is unknown.ResultsWe demonstrate that adaptation of mouse embryonic fibroblast, MEFS, to cell culture results in a rapid reprogramming of epigenetic and transcriptional states. We observed global 5-hydroxymethylcytosine (5hmC) erasure within three days of culture initiation. Loss of genic 5hmC was independent of global 5-methylcytosine (5mC) levels and could be partially rescued by addition of Vitamin C. Significantly, 5hmC loss was not linked to concomitant changes in transcription. Discrete promoter-specific gains of 5mC were also observed within seven days of culture initiation. Against this background of global 5hmC loss we identified a handful of developmentally important genes that maintained their 5hmC profile in culture, including the imprinted loci Gnas and H19. Similar outcomes were identified in the adaption of CD4+ T-cells to culture.ConclusionsWe report a dramatic and novel consequence of adaptation of mammalian cells to culture in which global loss of 5hmC occurs; suggesting rapid concomitant loss of methylcytosine dioxygenase activity. The observed epigenetic and transcriptional re-programming occurs much earlier than previously assumed, and has significant implications for the use of cell lines as faithful mimics of in vivo epigenetic and physiological processes.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2015. Vol. 16, s. 11-
Nationell ämneskategori
Annan klinisk medicin
Identifikatorer
URN: urn:nbn:se:liu:diva-115295DOI: 10.1186/s13059-014-0576-yISI: 000351819300001PubMedID: 25648825OAI: oai:DiVA.org:liu-115295DiVA, id: diva2:794706
Anmärkning

We thank Professors Adrian Bird and Nicholas Hastie for their comments on our manuscript. JT and RO are funded by IMI-MARCAR (under grant agreement number (115001) (MARCAR project)). Work in RM's lab is supported by the MRC, IMI-MARCAR and the BBSRC. This work in RM's lab was also initially funded by the Breakthrough Breast Cancer charity. Work in MB's lab was supported by Linkoping University strategic research funding and the Ake Wibergs fund (3772738). Work in SP's lab is supported by the BBSRC.

Tillgänglig från: 2015-03-12 Skapad: 2015-03-12 Senast uppdaterad: 2017-12-04Bibliografiskt granskad

Open Access i DiVA

fulltext(2561 kB)195 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2561 kBChecksumma SHA-512
20b29bc589e4362fed9d6244675739be009630c254764b29b24bad5ab66ec0b657857be12d4dce6be71798cb5f8c458bbdc6ebd377a5ddc6436285f7e1c2e568
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Nestor, Colm ELentini, AntonioBenson, Mikael

Sök vidare i DiVA

Av författaren/redaktören
Nestor, Colm ELentini, AntonioBenson, Mikael
Av organisationen
Avdelningen för kliniska vetenskaperHälsouniversitetetAllergicentrum US
I samma tidskrift
Genome Biology
Annan klinisk medicin

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 195 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 416 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf