Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic.
Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic.
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DOI：
10.1371/journal.pone.0053478
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lefterov I
中科院分区：
文献类型：
--
作者：
Cronican AA;Fitz NF;Carter A;Saleem M;Shiva S;Barchowsky A;Koldamova R;Schug J;Lefterov I
饮用水中长期接触砷，尤其是在子宫内或围产期接触，会引发神经和认知功能障碍以及记忆损伤。几项流行病学研究表明，早期接触低至中等水平砷的儿童存在认知和学习缺陷，但对这些缺陷的致病机制或病因了解甚少。由于体内研究显示组蛋白乙酰化在认知表现和记忆形成中起作用，我们研究了产前接触砷是否会导致表观基因组图谱发生变化。我们让C57Bl6/J小鼠在受孕前1周开始至出生饮用含100μg/L砷的水，并应用染色质免疫沉淀结合高通量大规模平行测序（ChIP - seq）来评估暴露组和对照组小鼠后代的H3K9乙酰化模式。胚胎期接触砷导致H3K9整体低乙酰化，并且在暴露幼崽的大脑样本中，功能注释发生变化，Krüppel相关框（KRAB）转录因子具有极显著的代表性。我们还发现成年小鼠接触砷会损害空间和情景记忆以及恐惧条件反射表现。这是第一项证明以下内容的研究：a）产前接触砷的后代中H3K9乙酰化模式在全基因组范围内的变化，以及b）成年小鼠中度砷暴露与认知障碍之间的联系。研究结果还强调了下一代测序方法在旨在揭示胚胎发育过程中除饮食限制外的环境因素通过组蛋白修饰在发育重编程中作用的研究中的适用性。
Chronic exposure to arsenic in drinking water, especially in utero or perinatal exposure, can initiate neurological and cognitive dysfunction, as well as memory impairment. Several epidemiological studies have demonstrated cognitive and learning deficits in children with early exposure to low to moderate levels of arsenic, but pathogenic mechanisms or etiology for these deficits are poorly understood. Since in vivo studies show a role for histone acetylation in cognitive performance and memory formation, we examined if prenatal exposure to arsenic causes changes in the epigenomic landscape. We exposed C57Bl6/J mice to 100 μg/L arsenic in the drinking water starting 1 week before conception till birth and applied chromatin immunoprecipitation followed by high-throughput massive parallel sequencing (ChIP-seq) to evaluate H3K9 acetylation pattern in the offspring of exposed and control mice. Arsenic exposure during embryonic life caused global hypo-acetylation at H3K9 and changes in functional annotation with highly significant representation of Krüppel associated box (KRAB) transcription factors in brain samples from exposed pups. We also found that arsenic exposure of adult mice impaired spatial and episodic memory, as well as fear conditioning performance. This is the first study to demonstrate: a) genome wide changes in H3K9 acetylation pattern in an offspring prenatally exposed to arsenic, and b) a connection between moderate arsenic exposure and cognitive impairment in adult mice. The results also emphasize the applicability of Next Generation Sequencing methodology in studies aiming to reveal the role of environmental factors, other than dietary restriction, in developmental reprogramming through histone modifications during embryonic development.
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影响因子：
10.5
作者：
Friedman, JR;Fredericks, WJ;Rauscher, FJ
通讯作者：
Rauscher, FJ
影响因子：
8.3
作者：
Calderón, J;Navarro, ME;Díaz-Barriga, F
通讯作者：
Díaz-Barriga, F
影响因子：
3.8
作者：
Jin, YP;Sun, GF;Qu, L
通讯作者：
Qu, L
影响因子：
10.4
作者：
Hall M;Gamble M;Slavkovich V;Liu X;Levy D;Cheng Z;van Geen A;Yunus M;Rahman M;Pilsner JR;Graziano J
通讯作者：
Graziano J
DOI：
10.1016/j.jtemb.2012.03.012
发表时间：
2012-06
期刊：
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
影响因子：
--
作者：
Arita A;Shamy MY;Chervona Y;Clancy HA;Sun H;Hall MN;Qu Q;Gamble MV;Costa M
通讯作者：
Costa M