Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_F17FEA13EB14
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.
Périodique
Nucleic Acids Research
Auteur(s)
Majocchi S., Aritonovska E., Mermod N.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Statut éditorial
Publié
Date de publication
2014
Volume
42
Numéro
1
Pages
193-204
Langue
anglais
Résumé
In eukaryotic cells, transgene expression levels may be limited by an unfavourable chromatin structure at the integration site. Epigenetic regulators are DNA sequences which may protect transgenes from such position effect. We evaluated different epigenetic regulators for their ability to protect transgene expression at telomeres, which are commonly associated to low or inconsistent expression because of their repressive chromatin environment. Although to variable extents, matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE) and the chicken cHS4 insulator acted as barrier elements, protecting a telomeric-distal transgene from silencing. MARs also increased the probability of silent gene reactivation in time-course experiments. Additionally, all MARs improved the level of expression in non-silenced cells, unlike other elements. MARs were associated to histone marks usually linked to actively expressed genes, especially acetylation of histone H3 and H4, suggesting that they may prevent the spread of silencing chromatin by imposing acetylation marks on nearby nucleosomes. Alternatively, an UCOE was found to act by preventing deposition of repressive chromatin marks. We conclude that epigenetic DNA elements used to enhance and stabilize transgene expression all have specific epigenetic signature that might be at the basis of their mode of action.
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2014 12:45
Dernière modification de la notice
20/08/2019 16:18
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