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001-es BibID:	BIBFORM095689
035-os BibID:	(WoS)000684852400006 (Scopus)85111011996
Első szerző:	Miskei Márton (molekuláris biológus, genetikus)
Cím:	Genome-wide mapping of binding sites of the transposase-derived SETMAR protein in the human genome / Márton Miskei, Adrienn Horváth, Lívia Viola, Laura Varga, Éva Nagy, Orsolya Feró, Zsolt Karányi, Jason Roszik, Csaba Miskey, Zoltán Ivics, Lóránt Székvölgyi
Dátum:	2021
ISSN:	2001-0370
Megjegyzések:	Throughout evolution, DNA transposons provide a recurrent supply of genetic information to give rise to novel gene functions by fusion of their transposase domain to various domains of host-encoded proteins. One of these "domesticated", transposase-derived factors is SETMAR/Metnase which is a naturally occurring fusion protein that consists of a histone-lysine methyltransferase domain and an HsMar1 transposase. To elucidate the biological role of SETMAR, it is crucial to identify genomic targets to which SETMAR specifically binds and link these sites to the regulation of gene expression. Herein, we mapped the genomic landscape of SETMAR binding in a near-haploid human leukemia cell line (HAP1) in order to identify on-target and off-target binding sites at high resolution and to elucidate their role in terms of gene expression. Our analysis revealed a perfect correlation between SETMAR and inverted terminal repeats (ITRs) of HsMar1 transposon remnants, which are considered as natural target sites for SETMAR binding. However, we did not detect any untargeted events at non-ITR sequences, calling into question previously proposed off-target binding sites. We identified sequence fidelity of the ITR motif as a key factor for determining the binding affinity of SETMAR for chromosomes, as higher conservation of ITR sequences resulted in increased affinity for chromatin and stronger repression of SETMAR-bound gene loci. These associations highlight how SETMAR's chromatin binding fine-tune gene regulatory networks in human tumour cells.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk SETMAR/Metnase transposase histone methyltransferase ChIP-seq
Megjelenés:	Computational and Structural Biotechnology Journal. - 19 (2021), p. 4032-4041. -
További szerzők:	Horváth Adrienn Viola Lívia Varga Laura Nagy Éva (1980-) (molekuláris biológus) Feró Orsolya Karányi Zsolt (1961-) (biostatisztikus, bioinformatikus) Roszik, Jason Miskey Csaba Ivics Zoltán (1964-) (biológus) Székvölgyi Lóránt (1977-) (biofizikus, biokémikus, sejtbiológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00024 GINOP NKFIH-NNE-130913 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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