Inhibiting eukaryotic transcription: Which compound to choose? How to evaluate its activity?
Olivier Bensaude
- Vol. 2, Iss: 3, pp 103-108
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TLDR
New compounds such as triptolide are fast, selective and completely arrest transcription as they trigger rapid degradation of RNAP II and α-amanitin, the characteristics and mechanisms of commonly used inhibitors are reviewed.Abstract:
This review deals first with general questions: how to evaluate transcription inhibition, describe changes in nuclear structure due to transcription inhibition, report on genes that are paradoxically stimulated by transcription inhibition. Next, it reviews the characteristics and mechanisms of commonly used inhibitors. α-amanitin is highly selective for RNAP II and RNAP III but its action is slow, actinomycin D is fast but its selectivity is poor, CDK9 inhibitors such as DRB, flavopiridol, are fast and reversible but many genes escape transcription inhibition. New compounds such as triptolide are fast, selective and completely arrest transcription as they trigger rapid degradation of RNAP II.read more
Citations
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Journal ArticleDOI
Mediator and RNA polymerase II clusters associate in transcription-dependent condensates
Won-Ki Cho,Jan-Hendrik Spille,Micca Hecht,Choongman Lee,Charles H. Li,Valentin Grube,Valentin Grube,Ibrahim I Cisse +7 more
TL;DR: This work used live-cell superresolution and light-sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly and suggests that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.
Journal ArticleDOI
Organizational principles of 3D genome architecture
TL;DR: Observations suggest that the 3D organization of the genome is an emergent property of chromatin and its components, and thus may not be only a determinant but also a consequence of its function.
Journal ArticleDOI
Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms
Olivia Padovan-Merhar,Gautham Nair,Andrew G. Biaesch,Andreas Mayer,Steven Scarfone,Shawn W. Foley,Angela Ruohao Wu,L. Stirling Churchman,Abhyudai Singh,Arjun Raj +9 more
TL;DR: It is shown that transcript abundance correlates with cellular volume at the single-cell level due to increased global transcription in larger cells, and a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S phase is revealed.
Journal ArticleDOI
Real-Time Dynamics of RNA Polymerase II Clustering in Live Human Cells
Ibrahim I Cisse,Ibrahim I Cisse,Ignacio Izeddin,Sebastien Causse,Lydia Boudarene,Adrien Senecal,Adrien Senecal,Leila Muresan,Claire Dugast-Darzacq,Claire Dugast-Darzacq,Bassam Hajj,Maxime Dahan,Maxime Dahan,Maxime Dahan,Xavier Darzacq,Xavier Darzacq +15 more
TL;DR: A quantitative single-cell approach to characterize protein spatiotemporal organization, with single-molecule sensitivity in live eukaryotic cells, suggests that transient crowding of enzymes may aid in rate-limiting steps of gene regulation.
Journal ArticleDOI
Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide
TL;DR: The results show that it is the transcriptional state that governs PRC2 binding, and it is proposed that it binds by default to nontranscribed CGI genes to maintain their silenced state and to protect cell identity.
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