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Series GSE57628 Query DataSets for GSE57628
Status Public on Apr 12, 2016
Title Study of Topoisomerase I in human
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary We report a mechanism through which the transcription machinery directly controls topoisomerase 1 (TOP1) activity to adjust DNA topology throughout the transcription cycle. By comparing TOP1 occupancy using ChIP-Seq, versus TOP1 activity using TOP1-Seq, a method reported here to map catalytically engaged TOP1, TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. TOP1 stimulation is strongly dependent on the kinase activity of BRD4, a protein that phosphorylates Ser2-CTD and regulates RNAPII pause-release. Thus the coordinated action of BRD4 and TOP1 overcame the torsional stress opposing transcription as RNAPII commenced elongation, but preserved negative supercoiling that assists promoter melting at start sites. This nexus between transcription and DNA topology promises to elicit new strategies to intercept pathological gene expression.
Overall design Examination of RNAPII and BRD4 by ChIP-Seq, Topoisimerase I by ChIP-Seq and Top1-Seq, and transcriptome expression by RNA-Seq in human colon cancer cells HCT116 (wt, wt+CPT, wt+JQ1, kiTop, kiTop1+JQ1, and siTop1).
Contributor(s) Baranello L, Wojtowicz D, Kouzine F, Cui K, Chan-Salis KY, Devaiah BN, Singer D, Pommier Y, Pugh BF, Przytycka TM, Lewis BA, Zhao K, Levens D
Citation(s) 27058666
BioProject PRJNA246370
Submission date May 13, 2014
Last update date May 15, 2019
Contact name Damian Wojtowicz
Phone 3014963713
Organization name NCBI/NLM/NIH
Street address 8600 Rockville Pike; Rm 8N811N
City Bethesda
State/province MD
ZIP/Postal code 20894
Country USA
Platforms (2)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
GPL9520 AB SOLiD System (Homo sapiens)
Samples (27)
GSM1385712 HCT116_wt_PolII_ChIPSeq
GSM1385713 HCT116_wt_+CPT_PolII_ChIPSeq
GSM1385714 HCT116_siTop1_PolII_ChIPSeq
SRA SRP041742

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Supplementary file Size Download File type/resource
GSE57628_RAW.tar 8.4 Gb (http)(custom) TAR (of TXT, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data included within Sample table
Processed data provided as supplementary file

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