Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse Balb c/J offspring subjected to postnatal handling vs. controls

ABSTRACT: Postnatal handling in rodents leads to decreased anxiety-like behavior in adulthood. We used microarrays to look at gene expression differences in the CA1 region of the hippocampus in female mice subjected to postnatal handling compared to controls. Experiment Overall Design: Balb c/J offspring were briefly separated from mothers for 15 minutes each morning on postnatal days 1-14 (handled group) or left undisturbed. At 8 weeks of age mice were tested in the open-field and light-dark behavioral paradigms to verify a handling-induced behavioral phenotype. 2 weeks after behavioral testing, animals were sacrificed and the CA1 region was microdissected. CA1 regions were stored at -20C in RNA later. RNA was extracted from 8 samples (4 handled and 4 non-handled) using Trizol. RNA was extracted from second group of animals (7 handled and 10 non-handled) using Qiagen RNA/DNA columns. All total RNA samples were double round amplied and labeled using standard Affymetrix protocols and hybridized to Mouse 430_2.0 arrays in parallel.

ORGANISM(S): Mus musculus

SUBMITTER: mark alter

PROVIDER: E-GEOD-11679 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.

Alter Mark D MD Rubin Daniel B DB Ramsey Keri K Halpern Rebecca R Stephan Dietrich A DA Abbott L F LF Hen Rene R

PloS one 20081006 10

<h4>Background</h4>Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors-DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence-are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in ...[more]

PMID: 18836535

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Project description:Intracellular calcium (Ca2+) overload is known to play a critical role in the development of cardiac dysfunction. Despite the remarkable improvement in managing the progression of heart disease, developing effective therapies for heart failure (HF) remains a challenge. A better understanding of molecular mechanisms that maintain proper Ca2+ levels and contractility in the injured heart could be of therapeutic value. Here, we report that the transcription factor Zinc finger E-box-binding homeobox2 (ZEB2) is induced by Hypoxia-inducible factor 1-alpha (HIF1a) in hypoxic cardiomyocytes and regulates a network of genes involved in Ca2+-handling and contractility during ischemic heart disease. Gain- and loss-of-function studies in genetic mouse models revealed ZEB2 in cardiomyocytes to be necessary and sufficient to protect the heart against ischemia-induced diastolic dysfunction and structural remodeling. Moreover, RNA sequencing (RNA-seq) of ZEB2-overexpressing (Zeb2 cTg) hearts post-injury implicated ZEB2 in regulating numerous Ca2+-handling and contractility-related genes. Mechanistically, ZEB2 overexpression increased the phosphorylation of phospholamban (PLN) at both serine-16 and threonine-17, implying enhanced activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), thereby augmenting SR Ca2+ uptake and contractility. Furthermore, we observed a decrease in the activity of Ca2+-dependent calcineurin/NFAT signaling in Zeb2 cTg hearts, which is the main driver of pathological cardiac remodeling. On a post-transcriptional level, we showed that ZEB2 expression can be regulated by the cardiomyocyte-specific microRNA-208a (miR-208a). Blocking the function of miR-208a with antimiR-208a increased ZEB2 expression in the heart and effectively protected from the development of pathological cardiac hypertrophy. Together, we present ZEB2 as a central regulator of contractility and Ca2+-handling components in the mammalian heart. Further mechanistic understanding of the role of ZEB2 in regulating Ca2+ homeostasis in cardiomyocytes is an essential step towards the development of improved therapies for HF.

Dataset Information

Transcription profiling of mouse Balb c/J offspring subjected to postnatal handling vs. controls

Publications

Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.

Similar Datasets

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