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Skalska, L.* ; Begley, V.* ; Beltran, M.* ; Lukauskas, S. ; Khandelwal, G.* ; Faull, P.* ; Bhamra, A.* ; Tavares, M.* ; Wellman, R.* ; Tvardovskiy, A. ; Foster, B. ; Ruiz de Los Mozos, I.* ; Herrero, J.* ; Surinova, S.* ; Snijders, A.P.* ; Bartke, T. ; Jenner, R.G.*

Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin.

Mol. Cell 81, 2944-2959.e10 (2021)
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A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonized the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors, including BAF, NuRD, EHMT1, and INO80 and inhibited their interaction with nucleosomes. The transcriptional elongation factor P-TEFb directly bound pre-mRNA, and its recruitment to chromatin upon Pol II inhibition was regulated by the 7SK ribonucleoprotein complex. We postulate that by antagonizing the interaction of regulatory proteins with chromatin, nascent RNA links transcriptional output with chromatin composition.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Rna Polymerase Ii ; Rnase ; Chromatin ; Histone Modification ; Nascent Rna ; Nucleosome ; Nucleosome Remodeller ; Pre-mrna ; Transcription Factor ; Transcriptional Elongation; Repressive Complex 2; Polymerase-ii; P-tefb; Pervasive Transcription; Binding Protein; Snrnp Complex; Web Server; 7sk Snrnp; Hiv-1 Tat; Gene
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 81, Issue: 14, Pages: 2944-2959.e10 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Grants Helmholtz Society
Worldwide Cancer Research
Blood Cancer UK
European Research Council (ERC)
Cancer Research UK Cancer Immunotherapy Network Accelerator (CITA)
Proteomics Research TTP - Cancer Research UK-UCL Centre
UCL Bill Lyons Informatics Centre - Cancer Research UK-UCL Centre
UCL Cancer Institute Genomics TTP