PMID- 20360682
OWN - NLM
STAT- MEDLINE
DCOM- 20100602
LR  - 20220716
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 29
IP  - 8
DP  - 2010 Apr 21
TI  - High-resolution profiling of gammaH2AX around DNA double strand breaks in the 
      mammalian genome.
PG  - 1446-57
LID - 10.1038/emboj.2010.38 [doi]
AB  - 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.
FAU - Iacovoni, Jason S
AU  - Iacovoni JS
AD  - Bioinformatic Plateau IFR150, INSERM, Toulouse, France.
FAU - Caron, Pierre
AU  - Caron P
FAU - Lassadi, Imen
AU  - Lassadi I
FAU - Nicolas, Estelle
AU  - Nicolas E
FAU - Massip, Laurent
AU  - Massip L
FAU - Trouche, Didier
AU  - Trouche D
FAU - Legube, Gaelle
AU  - Legube G
LA  - eng
GR  - F31 CA260794/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100401
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (H2AX protein, human)
RN  - 0 (Histones)
SB  - IM
MH  - Cell Line
MH  - *Chromosome Mapping
MH  - *DNA Breaks, Double-Stranded
MH  - Histones/*genetics/metabolism
MH  - Humans
MH  - Phosphorylation
MH  - Restriction Mapping
MH  - Transcription, Genetic
PMC - PMC2868577
COIS- The authors declare that they have no conflict of interest.
EDAT- 2010/04/03 06:00
MHDA- 2010/06/03 06:00
PMCR- 2011/04/21
CRDT- 2010/04/03 06:00
PHST- 2009/10/23 00:00 [received]
PHST- 2010/02/19 00:00 [accepted]
PHST- 2010/04/03 06:00 [entrez]
PHST- 2010/04/03 06:00 [pubmed]
PHST- 2010/06/03 06:00 [medline]
PHST- 2011/04/21 00:00 [pmc-release]
AID - emboj201038 [pii]
AID - 10.1038/emboj.2010.38 [doi]
PST - ppublish
SO  - EMBO J. 2010 Apr 21;29(8):1446-57. doi: 10.1038/emboj.2010.38. Epub 2010 Apr 1.