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

Lenka Skalska; Victoria Begley; Manuel Beltran; Saulius Lukauskas; Garima Khandelwal; Peter Faull; Amandeep Bhamra; Manuel Tavares; Rachel Wellman; Andrey Tvardovskiy; Benjamin M. Foster; Igor Ruiz de los Mozos; Javier Herrero; Silvia Surinova; Ambrosius P. Snijders; Till Bartke; Richard G. Jenner

doi:10.1016/j.molcel.2021.05.026

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

Lenka Skalska, Victoria Begley, Manuel Beltran, Saulius Lukauskas, Garima Khandelwal, Peter Faull, Amandeep Bhamra, Manuel Tavares, Rachel Wellman, Andrey Tvardovskiy, Benjamin M. Foster, Igor Ruiz de los Mozos, Javier Herrero, Silvia Surinova, Ambrosius P. Snijders, Till Bartke, Richard G. Jenner^*

^*Corresponding author for this work

PCE - Proteomics Center of Excellence

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2944-2959.e10
Journal	Molecular cell
Volume	81
Issue number	14
DOIs	https://doi.org/10.1016/j.molcel.2021.05.026
State	Published - Jul 15 2021

Keywords

RNA polymerase II
RNAse
chromatin
histone modification
nascent RNA
nucleosome
nucleosome remodeller
pre-mRNA
transcription factor
transcriptional elongation

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2021.05.026

Cite this

Skalska, L., Begley, V., Beltran, M., Lukauskas, S., Khandelwal, G., Faull, P., Bhamra, A., Tavares, M., Wellman, R., Tvardovskiy, A., Foster, B. M., Ruiz de los Mozos, I., Herrero, J., Surinova, S., Snijders, A. P., Bartke, T., & Jenner, R. G. (2021). Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin. Molecular cell, 81(14), 2944-2959.e10. https://doi.org/10.1016/j.molcel.2021.05.026

@article{cbf27b910995497a80f4ab4281d73ae4,

title = "Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin",

abstract = "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.",

keywords = "RNA polymerase II, RNAse, chromatin, histone modification, nascent RNA, nucleosome, nucleosome remodeller, pre-mRNA, transcription factor, transcriptional elongation",

author = "Lenka Skalska and Victoria Begley and Manuel Beltran and Saulius Lukauskas and Garima Khandelwal and Peter Faull and Amandeep Bhamra and Manuel Tavares and Rachel Wellman and Andrey Tvardovskiy and Foster, {Benjamin M.} and {Ruiz de los Mozos}, Igor and Javier Herrero and Silvia Surinova and Snijders, {Ambrosius P.} and Till Bartke and Jenner, {Richard G.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jul,

day = "15",

doi = "10.1016/j.molcel.2021.05.026",

language = "English (US)",

volume = "81",

pages = "2944--2959.e10",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "14",

}

Skalska, L, Begley, V, Beltran, M, Lukauskas, S, Khandelwal, G, Faull, P, Bhamra, A, Tavares, M, Wellman, R, Tvardovskiy, A, Foster, BM, Ruiz de los Mozos, I, Herrero, J, Surinova, S, Snijders, AP, Bartke, T & Jenner, RG 2021, 'Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin', Molecular cell, vol. 81, no. 14, pp. 2944-2959.e10. https://doi.org/10.1016/j.molcel.2021.05.026

TY - JOUR

T1 - Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin

AU - Skalska, Lenka

AU - Begley, Victoria

AU - Beltran, Manuel

AU - Lukauskas, Saulius

AU - Khandelwal, Garima

AU - Faull, Peter

AU - Bhamra, Amandeep

AU - Tavares, Manuel

AU - Wellman, Rachel

AU - Tvardovskiy, Andrey

AU - Foster, Benjamin M.

AU - Ruiz de los Mozos, Igor

AU - Herrero, Javier

AU - Surinova, Silvia

AU - Snijders, Ambrosius P.

AU - Bartke, Till

AU - Jenner, Richard G.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - 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.

AB - 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.

KW - RNA polymerase II

KW - RNAse

KW - chromatin

KW - histone modification

KW - nascent RNA

KW - nucleosome

KW - nucleosome remodeller

KW - pre-mRNA

KW - transcription factor

KW - transcriptional elongation

UR - http://www.scopus.com/inward/record.url?scp=85109482730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85109482730&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2021.05.026

DO - 10.1016/j.molcel.2021.05.026

M3 - Article

C2 - 34166609

AN - SCOPUS:85109482730

SN - 1097-2765

VL - 81

SP - 2944-2959.e10

JO - Molecular cell

JF - Molecular cell

IS - 14

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this