Genomics

Dataset Information

301

Whole-genome landscape of histone H2AX and γ-H2AX


ABSTRACT: Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous origin in replicating cells included telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with γ-H2AX of endogenous origin. γ-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous γ-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Subtelomeres were not responsive to external DNA damage. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy. Profiles of H2AX and gamma-H2AX in normal resting and cancer T cells with and without ionizing irradiation.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jung-Kyoon Choi   Jung Kyoon Choi 

PROVIDER: E-GEOD-25577 | ArrayExpress | 2012-04-03

SECONDARY ACCESSION(S): GSE25577SRP004653PRJNA133889

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells.

Seo Jungmin J   Kim Sang Cheol SC   Lee Heun-Sik HS   Kim Jung Kyu JK   Shon Hye Jin HJ   Salleh Nur Lina Mohd NL   Desai Kartiki Vasant KV   Lee Jae Ho JH   Kang Eun-Suk ES   Kim Jin Sung JS   Choi Jung Kyoon JK  

Nucleic acids research 20120329 13


Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous o  ...[more]

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