Limits...
Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration.

Aranyi T, Stockholm D, Yao R, Poinsignon C, Wiart T, Corre G, Touleimat N, Tost J, Galy A, Paldi A - Epigenetics Chromatin (2016)

Bottom Line: The effects of LV on target cells are expected to be limited to gene delivery.This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette.Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response.

View Article: PubMed Central - PubMed

Affiliation: Université Evry Val d'Essonne, UMRS_951, Genethon, 91002 Evry, France.

ABSTRACT

Background: Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The effects of LV on target cells are expected to be limited to gene delivery. Yet, human hematopoietic CD34+ cells respond to functional LVs as well as several types of non-integrating LVs by genome-wide DNA methylation changes.

Results: A new algorithm for the analysis of 450K Illumina data showed that these changes were marked by de novo methylation. The same 4126 cytosines located in islands corresponding to 1059 genes were systematically methylated. This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette. Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response.

Conclusion: These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome.

No MeSH data available.


Genomic localization of the CM-CpG-s. a Distribution of all CpG-s interrogated by the array according to their sequence context as provided by the manufacturer. b Sequence environment of the CM-CpG-s
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Fig4: Genomic localization of the CM-CpG-s. a Distribution of all CpG-s interrogated by the array according to their sequence context as provided by the manufacturer. b Sequence environment of the CM-CpG-s

Mentions: The majority (86 %) of the 4126 common modified CpG sites were found in CpG islands (CGI) (Fig. 4) in gene promoters, 5′UTRs, 1st exons and enhancers of 1059 genes (Additional file 2). The CpG-s in island “shores”, “shelves” or at non-assigned positions were strikingly underrepresented on our list (Fig. 4). The preferential localization of the CM-CpG-s to islands explains the high χ2 score obtained when the clustered distribution of the modifications were calculated (Fig. 2b).Fig. 4


Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration.

Aranyi T, Stockholm D, Yao R, Poinsignon C, Wiart T, Corre G, Touleimat N, Tost J, Galy A, Paldi A - Epigenetics Chromatin (2016)

Genomic localization of the CM-CpG-s. a Distribution of all CpG-s interrogated by the array according to their sequence context as provided by the manufacturer. b Sequence environment of the CM-CpG-s
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940770&req=5

Fig4: Genomic localization of the CM-CpG-s. a Distribution of all CpG-s interrogated by the array according to their sequence context as provided by the manufacturer. b Sequence environment of the CM-CpG-s
Mentions: The majority (86 %) of the 4126 common modified CpG sites were found in CpG islands (CGI) (Fig. 4) in gene promoters, 5′UTRs, 1st exons and enhancers of 1059 genes (Additional file 2). The CpG-s in island “shores”, “shelves” or at non-assigned positions were strikingly underrepresented on our list (Fig. 4). The preferential localization of the CM-CpG-s to islands explains the high χ2 score obtained when the clustered distribution of the modifications were calculated (Fig. 2b).Fig. 4

Bottom Line: The effects of LV on target cells are expected to be limited to gene delivery.This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette.Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response.

View Article: PubMed Central - PubMed

Affiliation: Université Evry Val d'Essonne, UMRS_951, Genethon, 91002 Evry, France.

ABSTRACT

Background: Lentiviral vectors (LV) are widely used for various gene transfer or gene therapy applications. The effects of LV on target cells are expected to be limited to gene delivery. Yet, human hematopoietic CD34+ cells respond to functional LVs as well as several types of non-integrating LVs by genome-wide DNA methylation changes.

Results: A new algorithm for the analysis of 450K Illumina data showed that these changes were marked by de novo methylation. The same 4126 cytosines located in islands corresponding to 1059 genes were systematically methylated. This effect required cellular entry of the viral particle in the cells but not the genomic integration of the vector cassette. Some LV preparations induced only mild sporadic changes while others had strong effects suggesting that LV batch heterogeneity may be related to the extent of the epigenetic response.

Conclusion: These findings identify a previously uncharacterized but consistent cellular response to viral components and provide a novel example of environmentally modified epigenome.

No MeSH data available.