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001-es BibID:	BIBFORM072900
035-os BibID:	(Cikkazonosító)12734 (WOS)000412491500006 (Scopus)85030764085
Első szerző:	Imre László (biológus)
Cím:	Nucleosome stability measured in situ by automated quantitative imaging / László Imre, Zoltán Simándi, Attila Horvath, György Fenyofalvi, Péter Nanasi Jr., Erfaneh Firouzi Niaki, Éva Hegedus, Zsolt Bacso, Urbain Weyemi, Rebekka Mauser, Juan Ausio, Albert Jeltsch, William Bonner, László Nagy, Hiroshi Kimura, Gábor Szabo
Dátum:	2017
ISSN:	2045-2322
Megjegyzések:	Current approaches have limitations in providing insight into the functional properties of particular nucleosomes in their native molecular environment. Here we describe a simple and powerful method involving elution of histones using intercalators or salt, to assess stability features dependent on DNA superhelicity and relying mainly on electrostatic interactions, respectively, and measurement of the fraction of histones remaining chromatin-bound in the individual nuclei using histone type- or posttranslational modification- (PTM-) specific antibodies and automated, quantitative imaging. The method has been validated in H3K4me3 ChIP-seq experiments, by the quantitative assessment of chromatin loop relaxation required for nucleosomal destabilization, and by comparative analyses of the intercalator and salt induced release from the nucleosomes of different histones. The accuracy of the assay allowed us to observe examples of strict association between nucleosome stability and PTMs across cell types, differentiation state and throughout the cell-cycle in close to native chromatin context, and resolve ambiguities regarding the destabilizing effect of H2A.X phosphorylation. The advantages of the in situ measuring scenario are demonstrated via the marked effect of DNA nicking on histone eviction that underscores the powerful potential of topological relaxation in the epigenetic regulation of DNA accessibility.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Fluorescence imaging Nuclear organization Epigenetics Molekuláris Medicina
Megjelenés:	Scientific Reports. - 7 : 1 (2017), p. 1-15. -
További szerzők:	Simándi Zoltán (1984-) (Ph.D. hallgató, molekuláris biológus) Horváth Attila (1988-) (programtervező informatikus) Fenyőfalvi György Nánási Péter Pál ifj. (1987-) (sejtbiológus) Firouzi Niaki, Erfaneh Hegedűs Éva (1978-) (biofizikus) Bacsó Zsolt (1963-) (biofizikus) Weyemi, Urbain Mauser, Rebekka Ausio, Juan Jeltsch, Albert Bonner, William Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Kimura, Hiroshi Szabó Gábor (1953-) (biofizikus)
Pályázati támogatás:	K72762 OTKA NK101337 OTKA TÁMOP-4.2.2-08/1-2008-0015 TÁMOP TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP I. ABC transzporterek; II. Magasabbrendű kromatinszerkezet TÁMOP 4.2.2.A- 11/1/KONV-2012-0023 "VÉD-ELEM TÁMOP TÁMOP 4.2.4. A/2-11-1-2012-0001 TÁMOP GINOP-2.3.2-15-2016-00044 GINOP
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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
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