GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes.
BACKGROUND
The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown.


RESULTS
The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knock-down was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide microarrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGFbeta signalling and stress response.


CONCLUSIONS
Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation.
Bonin
Florian
F
Université de Lyon, Lyon, F-69003, France. bonin@crh1.org
Molina
Manuella
M
Malet
Claude
C
Ginestet
Chantal
C
Berthier-Vergnes
Odile
O
Martin
Michèle T
MT
Lamartine
Jérôme
J
D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D014161:Transduction, Genetic
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human