NDLI: DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus

Content Provider	PubMed Central
Author	Baranello, Laura Bertozzi, Davide Fogli, Maria Vittoria Pommier, Yves Giovanni, Capranico
Copyright Year	2009
Abstract	Top1 inhibition by camptothecin (CPT) perturbs RNA polymerase II (Pol II) density at promoters and along transcribed genes suggesting an involvement of Top1 in Pol II pausing. Here, we demonstrate that Top1 inhibition favors Pol II escape from a promoter-proximal pausing site of the human HIF-1α gene in living cells. Interestingly, alternative splicing at exon 11 was markedly altered in nascent HIF-1α mRNAs, and chromatin structure was also affected with enhanced histone acetylation and reduced nucleosome density in a manner dependent on cdk activity. Moreover, CPT increases transcription of a novel long RNA (5′aHIF1α), antisense to human HIF-1α mRNA, and a known antisense RNA at the 3′-end of the gene, while decreasing mRNA levels under normoxic and hypoxic conditions. The effects require Top1, but are independent from Top1-induced replicative DNA damage. Chromatin RNA immunoprecipitation results showed that CPT can activate antisense transcription mediated by cyclin-dependent kinase (cdk) activity. Thus, Top1 inhibition can trigger a transcriptional stress, involving antisense transcription and increased chromatin accessibility, which is dependent on cdk activity and deregulated Pol II pausing. A changed balance of antisense transcripts and mRNAs may then lead to altered regulation of HIF-1α activity in human cancer cells.
Related Links	http://dx.doi.org/10.1093/nar/gkp817
Ending Page	171
Page Count	13
Starting Page	159
File Format	PDF
ISSN	03051048
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	1
Volume Number	38
Language	English
Publisher	Oxford University Press
Publisher Date	2010-01-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus

Release of promoter–proximal paused Pol II in response to histone deacetylase inhibition

Topoisomerase IIβ Deficiency Enhances Camptothecin-induced Apoptosis

Role of DNA topoisomerase I in the transcription of supercoiled rRNA gene.

Transcription. Gene expression--where to start?

Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters.

Alternative DNA secondary structure formation affects RNA polymerase II promoter-proximal pausing in human

Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1α,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression

Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: Implications for physiological and therapeutic modulation of enzyme activity

DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus

Similar Documents

DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus

Release of promoter–proximal paused Pol II in response to histone deacetylase inhibition

Topoisomerase IIβ Deficiency Enhances Camptothecin-induced Apoptosis

Role of DNA topoisomerase I in the transcription of supercoiled rRNA gene.

Transcription. Gene expression--where to start?

Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters.

Alternative DNA secondary structure formation affects RNA polymerase II promoter-proximal pausing in human

Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1α,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression

Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: Implications for physiological and therapeutic modulation of enzyme activity

DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus