Regional genome transcriptional response of adult mouse brain to hypoxia

Xu, Huichun; Lu, Aiming; Sharp, Frank R.

doi:10.1186/1471-2164-12-499

Cited by 30 publications

(21 citation statements)

References 59 publications

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“…HIF1A is known to be transcriptionally regulated in fish (Liu et al 2013), and our identification of a trans -eQTL for HIF1A demonstrates that regulatory variation for this gene is present in Baltic Sea sticklebacks and could be an alternative, unexamined, target of selection. The proteins HNF4A, CNNB1, and HDAC3 are also involved in the hypoxia response (Xu et al 2011; Wang et al 2015). …”

Section: Discussionmentioning

confidence: 99%

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

Pritchard

Viitaniemi

McCairns

et al. 2017

G3 Genes|Genomes|Genetics

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Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located expression quantitative trait loci (eQTL) underlying the variation in gene expression in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis- and trans-regulatory regions. Trans-eQTL clustered into hotspots. We did not identify master transcriptional regulators in hotspot locations: rather, the presence of hotspots may be driven by complex interactions between multiple transcription factors. One observed hotspot colocated with a QTL recently found to underlie salinity tolerance in the threespine stickleback. However, most other observed hotspots did not colocate with regions of the genome known to be involved in adaptive divergence between marine and freshwater habitats.

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Section: Discussionmentioning

confidence: 99%

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

Pritchard

Viitaniemi

McCairns

et al. 2017

G3 Genes|Genomes|Genetics

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“…For these micro-array experiments we used complete cerebral hemispheres, thereby including different brain regions that might have counteracting gene expression, as was previously described in the adult mouse brain after hypoxic preconditioning [9]. The observed differences in gene expression across different brain regions might be related to their phylogenetic age or metabolic activity.…”

Section: Discussionmentioning

confidence: 99%

Fetal brain genomic reprogramming following asphyctic preconditioning

et al. 2013

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BackgroundFetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore we investigated whole genome differential gene expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 by reversibly clamping uterine circulation. Male control and FA offspring were sacrificed 96 h after FA preconditioning. Whole genome transcription was investigated with Affymetrix Gene1.0ST chip.ResultsData were analyzed with the Bioconductor Limma package, which showed 53 down-regulated and 35 up-regulated transcripts in the FA-group. We validated these findings with RT-qPCR for adh1, edn1, leptin, rdh2, and smad6. Moreover, we investigated differences in gene expression across different brain regions. In addition, we performed Gene Set Enrichment Analysis (GSEA) which revealed 19 significantly down-regulated gene sets, mainly involved in neurotransmission and ion transport. 10 Gene sets were significantly up-regulated, these are mainly involved in nucleosomal structure and transcription, including genes such as mecp2.ConclusionsHere we identify for the first time differential gene expression after asphyctic preconditioning in fetal brain tissue, with the majority of differentially expressed transcripts being down-regulated. The observed down-regulation of cellular processes such as neurotransmission and ion transport could represent a restriction in energy turnover which could prevent energy failure and subsequent neuronal damage in an asphyctic event. Up-regulated transcripts seem to exert their function mainly within the cell nucleus, and subsequent Gene Set Enrichment Analysis suggests that epigenetic mechanisms play an important role in preconditioning induced neuroprotection.

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“…7 days after ovariectomy and implantation of silastic tubing, oil- and E 2 -treated mice were placed in cages inside a hypoxia chamber (BioSpherix, Lacona, NY) that was equilibrated to 7% O 2 and 93% N 2 for 3 h, conditions which have been shown to induce substantial changes in mRNA expression [48]. Oxygen concentration was monitored continuously throughout the experiments.…”

Section: Methodsmentioning

confidence: 99%

17β-Estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia

Dietrich

Humphreys

Nardulli

2013

The Journal of Steroid Biochemistry and Molecular Biology

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While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemiainduced damage in the brain. Since E2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2.

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Regional genome transcriptional response of adult mouse brain to hypoxia

Cited by 30 publications

References 59 publications

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

Regulatory Architecture of Gene Expression Variation in the Threespine Stickleback Gasterosteus aculeatus

Fetal brain genomic reprogramming following asphyctic preconditioning

17β-Estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia

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