We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.
Transcriptional ontogeny of the developing liver.
Specimen part
View SamplesChanges in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and the plastic storage of memories. DREAM /KChIP proteins form heterotetramers that bind DNA and repress transcription in a Ca2+-dependent manner. Single ablation of one member of the DREAM/KChIP family may result in a mild or the absence of phenotype due to partial gene compensation. To study the function of DREAM/KChIP proteins in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). We show that daDREAM controls the expression of several activity-dependent transcription factors including Npas4, Nr4a1, Mef2C, JunB and c-Fos, as well as the chromatin modifying enzyme Mbd4 and proteins related to actin polymerization like Arc and gelsolin. Thus, directly or through these targets, expression of daDREAM in the forebrain resulted in a complex phenotype characterized by i) impaired learning and memory, ii) loss of recurrent inhibition and enhanced LTP in the dentate gyrus without affecting Kv4-mediated potassium currents, and iii) modified spine density in DG granule neurons. Our results propose DREAM as a master-switch transcription factor regulating several activity-dependent gene expression programs to control synaptic plasticity, learning and memory.
DREAM controls the on/off switch of specific activity-dependent transcription pathways.
Specimen part
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