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

• Published in: Molecular cell Vol. 81; no. 14; pp. 2944 - 2959.e10
• Main Authors: Skalska, Lenka, Begley, Victoria, Beltran, Manuel, Lukauskas, Saulius, Khandelwal, Garima, Faull, Peter, Bhamra, Amandeep, Tavares, Manuel, Wellman, Rachel, Tvardovskiy, Andrey, Foster, Benjamin M., Ruiz de los Mozos, Igor, Herrero, Javier, Surinova, Silvia, Snijders, Ambrosius P., Bartke, Till, Jenner, Richard G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2021
• Subjects: Animals; chromatin; Chromatin - metabolism; DNA-Binding Proteins - metabolism; Embryonic Stem Cells - metabolism; Gene Expression Regulation - physiology; HEK293 Cells; histone modification; Humans; Male; Mice; nascent RNA; nucleosome; nucleosome remodeller; nucleosomes; Nucleosomes - metabolism; Positive Transcriptional Elongation Factor B - metabolism; pre-mRNA; Protein Binding - physiology; proteomics; Proteomics - methods; ribonucleoproteins; RNA; RNA - metabolism; RNA polymerase II; RNA Polymerase II - metabolism; RNAse; transcription (genetics); transcription factor; Transcription Factors - metabolism; Transcription, Genetic - physiology; transcriptional elongation; transcriptional elongation factors; Transcriptional Elongation Factors - metabolism; RNAse; transcription factor; pre-mRNA; transcriptional elongation; histone modification; nucleosome remodeller; nucleosome; nascent RNA; chromatin; RNA polymerase II
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2021.05.026

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. [Display omitted] •Pol II inhibition induced recruitment of a set of regulatory proteins to chromatin•Many of these changes were also observed upon RNA degradation•RNA binds a set of chromatin modifiers and inhibits interaction with nucleosomes•P-TEFb binds pre-mRNA, and 7SK regulates its interaction with RNA and chromatin Nascent RNA interacts with a wide array of regulatory proteins but its impact on chromatin composition has not been assessed. Skalska and colleagues use proteomics methods to reveal that nascent RNA antagonizes the association of a set of regulatory proteins with chromatin.