GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes.
GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes.
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GATA3 是人类角质形成细胞对低剂量电离辐射转录反应的主要调节因子。
DOI：
10.1186/1471-2164-10-417
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发表时间：
2009-09-07
期刊：
影响因子：
4.4
通讯作者：
Lamartine J
中科院分区：
文献类型：
--
作者：
Bonin F;Molina M;Malet C;Ginestet C;Berthier-Vergnes O;Martin MT;Lamartine J
一般人群经常受到自然、职业或医疗辐射的低水平辐射。即使低水平辐射的生物效应已经被激烈争论和研究，细胞对低剂量反应的分子机制仍然很大程度上未知。本研究调查了 GATA3 蛋白在控制暴露于 1 cGy 剂量 X 射线的人类角质形成细胞的细胞和分子反应中的作用。染色质免疫沉淀显示 GATA3 能够结合响应 1 cGy 暴露的 4 个基因的启动子。为了进一步研究电离辐射暴露后 GATA3 的作用，我们研究了 GATA3 敲低细胞中辐射的细胞和分子后果。通过在分化的角质形成细胞中慢病毒介导的针对 GATA3 转录物的 shRNA 表达来实现敲低。首先，评估放射敏感性：发现 GATA3 敲低细胞中与 1 cGy 辐射相关的立即存活率（XTT 测试）毒性增加。还研究了 GATA3 敲低对 X 射线照射细胞转录组的影响，使用寡核苷酸微阵列评估正常背景与 GATA3 敲低背景下照射后 3 小时至 72 小时之间的变化；发现 GATA3 敲低细胞中的转录组反应完全改变，在辐射后 48 小时出现强烈的诱导/抑制峰值。功能注释揭示了已知参与伴侣活性、TGFβ信号传导和应激反应的基因的富集。总而言之，这些数据表明 GATA3 是表皮细胞对极低剂量辐射的细胞和分子反应的重要调节剂。
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. 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, TGFβ signalling and stress response. 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.
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影响因子：
3.5
作者：
Gagnoux-Palacios, L;Hervouet, C;Meneguzzi, G
通讯作者：
Meneguzzi, G
影响因子：
8
作者：
Martin, M;Vozenin, MC;Lefaix, JL
通讯作者：
Lefaix, JL
影响因子：
2.2
作者：
METTLER, FA;SINCLAIR, WK;RICKS, RC
通讯作者：
RICKS, RC
影响因子：
3.4
作者：
Slonina, Dorota;Biesaga, Beata;Kojs, Zbigniew
通讯作者：
Kojs, Zbigniew
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R