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001-es BibID:	BIBFORM077785
035-os BibID:	(Cikkazonosító)4889 (WOS)000461762600006 (Scopus)85063344159
Első szerző:	Ozgyin Lilla (molekuláris biológus)
Cím:	Extensive epigenetic and transcriptomic variability between genetically identical human B-lymphoblastoid cells with implications in pharmacogenomics research / Lilla Ozgyin, Attila Horvath, Zsuzsanna Hevessy, Balint L. Balint
Dátum:	2019
ISSN:	2045-2322
Megjegyzések:	Genotyped human B-lymphoblastoid cell lines (LCLs) are widely used models in mapping quantitative trait loci for chromatin features, gene expression, and drug response. The extent of genotype-independent functional genomic variability of the LCL model, although largely overlooked, may inform association study design. In this study, we use flow cytometry, chromatin immunoprecipitation sequencing and mRNA sequencing to study surface marker patterns, quantify genome-wide chromatin changes (H3K27ac) and transcriptome variability, respectively, among five isogenic LCLs derived from the same individual. Most of the studied LCLs were non-monoclonal and had mature B cell phenotypes. Strikingly, nearly one-fourth of active gene regulatory regions showed significantly variable H3K27ac levels, especially enhancers, among which several were classified as clustered enhancers. Large, contiguous genomic regions showed signs of coordinated activity change. Regulatory differences were mirrored by mRNA expression changes, preferentially affecting hundreds of genes involved in specialized cellular processes including immune and drug response pathways. Differential expression of DPYD, an enzyme involved in 5-fluorouracil (5-FU) catabolism, was associated with variable LCL growth inhibition mediated by 5-FU. The extent of genotype-independent functional genomic variability might highlight the need to revisit study design strategies for LCLs in pharmacogenomics.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Scientific Reports. - 9 (2019), p. 1-16. -
További szerzők:	Horváth Attila (1988-) (programtervező informatikus) Hevessy Zsuzsanna (1966-) (laboratóriumi szakorvos) Bálint Bálint László (1971-) (kutató orvos)
Pályázati támogatás:	GINOP-2.3.3-15-2016-00007 GINOP EFOP-3.6.1-16-2016-00022 EFOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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