Počet záznamů: 1
The chromatin landscape at the HIV-1 provirus integration site determines viral expression
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SYSNO ASEP 0559755 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The chromatin landscape at the HIV-1 provirus integration site determines viral expression Tvůrce(i) Vansant, G. (BE)
Chen, H.C. (FR)
Zorita, E. (ES)
Trejbalová, Kateřina (UMG-J) RID
Miklík, Dalibor (UMG-J)
Filion, G. (ES)
Debyser, Z. (BE)Celkový počet autorů 7 Zdroj.dok. Nucleic Acids Research. - : Oxford University Press - ISSN 0305-1048
Roč. 48, č. 14 (2020), s. 7801-7817Poč.str. 17 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova retrovirus integration ; HIV latency ; chromatin a LEDGF/p75 Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000574297400020 DOI 10.1093/nar/gkaa536 Anotace HIV-1 persists lifelong in memory cells of the immune system as latent provirus that rebounds upon treatment interruption. Therefore, the latent reservoir is the main target for an HIV cure. Here, we studied the direct link between integration site and transcription using LEDGINs and Barcoded HIV-ensembles (B-HIVE). LEDGINs are antivirals that inhibit the interaction between HIV-1 integrase and the chromatin tethering factor LEDGF/p75. They were used as a tool to retarget integration, while the effect on HIV expression was measured with B-HIVE. B-HIVE tracks insert-specific HIV expression by tagging a unique barcode in the HIV genome. We confirmed that LEDGINs retarget integration out of gene-dense and actively transcribed regions. The distance to H3K36me3, the marker recognized by LEDGF/p75, clearly increased. LEDGIN treatment reduced viral RNA expression and increased the proportion of silent provirus. Finally, silent proviruses obtained after LEDGIN treatment were located further away from epigenetic marks associated with active transcription. Interestingly, proximity to enhancers stimulated transcription irrespective of LEDGIN treatment, while the distance to H3K36me3 only changed after treatment with LEDGINs. The fact that proximity to these markers are associated with RNA expression support the direct link between provirus integration site and viral expression. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2023 Elektronická adresa https://academic.oup.com/nar/article/48/14/7801/5864711?login=true
Počet záznamů: 1