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Series GSE64467 Query DataSets for GSE64467
Status Public on Dec 23, 2017
Title ADP-ribose derived Nuclear ATP is Required for Chromatin Remodeling and Hormonal Gene Regulation
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Key nuclear processes in eukaryotes including DNA replication or repair and gene regulation require extensive chromatin remodeling catalyzed by energy consuming enzymes. How the energetic demands of such processes are ensured in response to rapid stimuli remains unclear. We have analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly-ADP-ribose to ADP-ribose. Nuclear ATP synthesis requires the combined enzymatic activities of PARP1, PARG and NUDIX5/NUDT5. Although initiated via mitochondrial derived ATP, the nuclear source of ATP is essential for hormone induced chromatin remodeling, gene regulation and cell proliferation and may also participate in DNA repair. This novel pathway reveals exciting avenues of research for drug development.
Overall design 1) Hormonal gene regulation requires synthesis of PAR and its degradation to ADPribose by PARG. 2) ADP-ribose is converted to ATP in the cell nuclei by hormone-activated NUDIX5/NUDT5. 3) Blocking nuclear ATP formation precludes hormone-induced chromatin remodeling, gene regulation and cell proliferation.
Contributor(s) Wright RH, Lioutas A, LeDily F, Soronellas D, Pohl A, Bonet J, Nacht AS, Samino S, Vicent GP, Wierer M, Trabado MA, Carolis C, Yanes O, Oliva B, Beato M
Citation(s) 27257257
Submission date Dec 23, 2014
Last update date May 15, 2019
Contact name Miguel Beato
Organization name CRG
Street address Aiguader 88
City Barcelona
ZIP/Postal code 08003
Country Spain
Platforms (2)
GPL9052 Illumina Genome Analyzer (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (9)
GSM1571861 ChIP-seq BPTF T0
GSM1571862 ChIP-seq BPTF T30
GSM1571863 ChIP-seq H2A T0
BioProject PRJNA271077
SRA SRP051504

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Supplementary file Size Download File type/resource
GSE64467_BPTF_hormone-displaced_peaks.hg19.txt.gz 48.5 Kb (ftp)(http) TXT
GSE64467_BPTF_hormone-recruited_peaks.hg19.txt.gz 16.8 Kb (ftp)(http) TXT
GSE64467_RAW.tar 1.5 Mb (http)(custom) TAR (of BED)
GSE64467_RPKM.H2A.hg19-proteinCoding-genes.txt.gz 525.5 Kb (ftp)(http) TXT
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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