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Genome-Wide Alteration of Histone H3K9 Acetylation Pattern in Mouse Offspring Prenatally Exposed to Arsenic

Cronican, AA and Fitz, NF and Carter, A and Saleem, M and Shiva, S and Barchowsky, A and Koldamova, R and Schug, J and Lefterov, I (2013) Genome-Wide Alteration of Histone H3K9 Acetylation Pattern in Mouse Offspring Prenatally Exposed to Arsenic. PLoS ONE, 8 (2).

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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. © 2013 Cronican et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Cronican, AAaas57@pitt.eduAAS57
Fitz, NFnffitz@pitt.eduNFFITZ
Carter, Aalexisc@pitt.eduALEXISC
Saleem, M
Shiva, Ssss43@pitt.eduSSS43
Barchowsky, Aaab20@pitt.eduAAB20
Koldamova, Rradak@pitt.eduRADAK
Schug, J
Lefterov, IILIYAL@pitt.eduILIYAL
Date: 6 February 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0053478
Schools and Programs: School of Public Health > Environmental and Occupational Health
School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Other ID: NLM PMC3566160
PubMed Central ID: PMC3566160
PubMed ID: 23405071
Date Deposited: 14 Mar 2013 14:43
Last Modified: 02 Feb 2019 16:55


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