Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. We identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region. To identify whether changes in H3K9me2 correlated with genome-wide alterations in gene expression in the NAc, we employed microarray analyses to examine gene expression profiles induced by a challenge dose of cocaine in animals with or without a history of prior cocaine exposure. Animals that had received repeated cocaine displayed dramatically increased gene expression 1 hour after a cocaine challenge in comparison to acutely treated animals. This increased gene expression still occurred in response to a cocaine challenge given after 1 week of withdrawal from repeated cocaine. These data suggest that repeated, but not acute, cocaine exposure results in persistent sensitized genomic responses to a cocaine challenge, indicating that sensitized behavioral responses to repeated cocaine are likely the result of G9a-dependent alterations in global transcriptional responses to cocaine.
Essential role of the histone methyltransferase G9a in cocaine-induced plasticity.
Specimen part
View SamplesMost higher organisms, including plants and animals, have developed a time-keeping mechanism that allows them to anticipate daily fluctuations of environmental parameters such as light and temperature. This circadian clock efficiently coordinates plant growth and metabolism with respect to time-of-day by producing self-sustained rhythms of gene expression with an approximately 24-hour period. The importance of these rhythms has in fact been demonstrated in both phytoplankton and higher plants: organisms that have an internal clock period matched to the external environment possess a competitive advantage over those that do not.
The circadian clock regulates auxin signaling and responses in Arabidopsis.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesPlant hypocotyls elongate in response to darkness. The response to darkness is gated by the circadian clock, such that wild-type plants (Col) only respond to darkness with growth once every 24 hours, whereas arrhythmic lines, such as CCA1-34, will respond to darkness with growth at any time of day. The experiment here was designed to find genes whose expression was correlated with growth. It should also pick up other genes that are gated by the circadian clock or that are direct targets of CCA1.
Rhythmic growth explained by coincidence between internal and external cues.
Age, Specimen part
View SamplesAnlaysis of the differential gene expression between T47D cells expressing wild type (WT) progesterone receptor isoform B (PR) or SUMOylation-deficient PR molecules.
Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesRecent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sex, Age, Specimen part, Disease stage, Race
View SamplesCutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in the U.S. annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). In order to identify potential targets for molecularly targeted chemoprevention, we performed integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar UV-driven Hairless mouse model. We identified the major transcriptional drivers of this sequence showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this UV-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. Overall design: We sought to identify important genetic events that drive squamous cell carcinoma development through combined analysis of next generation sequencing of matched patient samples with a UV-driven mouse model to identify key pathways.
Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.
Specimen part, Subject
View SamplesREST is a master regulator of genes that are involved in the acqusition of neuronal fate. The role of REST is not well understood so we attempted to investigate the role of REST in the development of neural cells by analysing the genes that are upregulated when REST is knocked down via shRNA
REST regulates the pool size of the different neural lineages by restricting the generation of neurons and oligodendrocytes from neural stem/progenitor cells.
Specimen part
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