title: High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome.
abstract: Chromatin acts as a key regulator of DNA-related processes such as DNA damage repair. Although ChIP-chip is a powerful technique to provide high-resolution maps of protein-genome interactions, its use to study DNA double strand break (DSB) repair has been hindered by the limitations of the available damage induction methods. We have developed a human cell line that permits induction of multiple DSBs randomly distributed and unambiguously positioned within the genome. Using this system, we have generated the first genome-wide mapping of gammaH2AX around DSBs. We found that all DSBs trigger large gammaH2AX domains, which spread out from the DSB in a bidirectional, discontinuous and not necessarily symmetrical manner. The distribution of gammaH2AX within domains is influenced by gene transcription, as parallel mappings of RNA Polymerase II and strand-specific expression showed that gammaH2AX does not propagate on active genes. In addition, we showed that transcription is accurately maintained within gammaH2AX domains, indicating that mechanisms may exist to protect gene transcription from gammaH2AX spreading and from the chromatin rearrangements induced by DSBs.
authors.affiliation: Bioinformatic Plateau IFR150, INSERM, Toulouse, France.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Iacovoni
authors.forename: Pierre
authors.initials: P
authors.lastname: Caron
authors.forename: Imen
authors.initials: I
authors.lastname: Lassadi
authors.forename: Estelle
authors.initials: E
authors.lastname: Nicolas
authors.forename: Laurent
authors.initials: L
authors.lastname: Massip
authors.forename: Didier
authors.initials: D
authors.lastname: Trouche
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Legube
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D053903:DNA Breaks, Double-Stranded; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D015183:Restriction Mapping; D014158:Transcription, Genetic
chemical_list: C468783:H2AX protein, human; D006657:Histones