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

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Serval ID
serval:BIB_F17FEA13EB14
Type
Article: article from journal or magazin.
Collection
Publications
Title
Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.
Journal
Nucleic Acids Research
Author(s)
Majocchi S., Aritonovska E., Mermod N.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
2014
Volume
42
Number
1
Pages
193-204
Language
english
Abstract
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
Yes
Create date
28/01/2014 12:45
Last modification date
20/08/2019 16:18
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