Universität zu Köln

Doerfler, Walter, Weber, Stefanie and Naumann, Anja (2018). Inheritable epigenetic response towards foreign DNA entry by mammalian host cells: a guardian of genomic stability. Epigenetics, 13 (12). S. 1141 - 1154. PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 1559-2308

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Abstract

Apart from its well-documented role in long-term promoter silencing, the genome-wide distribution patterns of similar to 28 million methylated or unmethylated CpG dinucleotides, e.g. in the human genome, is in search of genetic functions. We have set out to study changes in the cellular CpG methylation profile upon introducing foreign DNA into mammalian cells. As stress factors served the genomic integration of foreign (viral or bacterial plasmid) DNA, virus infections or the immortalization of cells with Epstein Barr Virus (EBV). In all instances investigated, alterations in cellular CpG methylation and transcription profiles were observed to different degrees. In the case of adenovirus DNA integration in adenovirus type 12 (Ad12)-transformed hamster cells, the extensive changes in cellular CpG methylation persisted even after the complete loss of all transgenomic Ad12 DNA. Hence, stress-induced alterations in CpG methylation can be inherited independent of the continued presence of the transgenome. Upon virus infections, changes in cellular CpG methylation appear early after infection. In EBV immortalized as compared to control cells, CpG hypermethylation in the far-upstream region of the human FMR1 promoter decreased four-fold. We conclude that in the wake of cellular stress due to foreign DNA entry, preexisting CpG methylation patterns were altered, possibly at specific CpG dinucleotides. Frequently, transcription patterns were also affected. As a working concept, we view CpG methylation profiles in mammalian genomes as a guarding sensor for genomic stability under epigenetic control. As a caveat towards manipulations of cells with foreign DNA, such cells can no longer be considered identical to their un-manipulated counterparts.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Doerfler, Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Naumann, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-199777
DOI:	10.1080/15592294.2018.1549463
Journal or Publication Title:	Epigenetics
Volume:	13
Number:	12
Page Range:	S. 1141 - 1154
Date:	2018
Publisher:	TAYLOR & FRANCIS INC
Place of Publication:	PHILADELPHIA
ISSN:	1559-2308
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSFORMED-CELLS; METHYLATION; ADENOVIRUS; SEQUENCES; GENE; TRANSCRIPTION; DESTABILIZATION; REPLICATION; INSTABILITY; INTEGRATION Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19977