DNA microarray analysis and functional profile of pituitary transcriptome under core-clock protein BMAL1 control
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29664 | GEO | 2011/12/31
SECONDARY ACCESSION(S): PRJNA141143
REPOSITORIES: GEO
Similar Datasets
Project description:To find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice Wild type and clock-deficient Bmal1-/- mice in the C57BL/6J were used at 8 to 12 weeks of age. All animals were housed in a 12-h light/12-h dark cycle (light/dark, 12:12). Mice were sacrificed by decapitation at ZT12 (light off), and three pools of three pituitaries per genotype were used to isolate total RNA. Pituitary glands taken from three mice from the same genotype were removed and frozen in liquid nitrogen until total RNA isolation.
2011-12-31 | E-GEOD-29664 | biostudies-arrayexpress
Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.
2020-02-17 | PXD009243 | Pride
Project description:The human osteosarcoma cell line U2OS contains a functional circadian clock but expresses only a few rhythmic genes. We identified by ChIP-seq analysis 3040 binding sites of the circadian transcription factors BMAL1, CLOCK, and CRY1 in the genome of U2OS cells, comparable to the number found in highly rhythmic tissues like liver. ChIP was performed as described previously (Rey et al, 2011; doi:10.1371/journal.pbio.1000595) using confluent desynchronized U2OS cells and BMAL1, CLOCK, and CRY1-antibodies. Immunoprecipitated chromatin (10 ng DNA of 8 independent BMAL1 ChIPs with enrichment levels > 80-fold, 9 ng DNA of a CRY1 ChIP with 10-fold enrichment, and 8 ng DNA of a CLOCK ChIP with 40-fold enrichment) was used for library preparation. Three lanes of the BMAL1 library, and one lane each of the CRY1 and CLOCK library were sequenced on the Illumina Genome Analyzer IIx using Single-Read Cluster Generation Kit and 36 Cycle Sequencing Kit v2 (Lausanne Genomics Technologies Facility).
2016-02-11 | E-GEOD-44236 | biostudies-arrayexpress
Project description:TMT analysis of proteomic changes in the gastrocnemius skeletal muscles of WT and Bmal1-KO mice, and Bmal1-KO mice rescued with AAV-mediated muscle-specific expression of Bmal1.
2024-10-03 | PXD054406 | Pride
Project description:The regulation of pituitary function via the hypothalamus and via intra-pituitary connections represents a complex system. Though hormones secreted from the pituitary glands have been well studied, overall information of proteins expressed in the pituitary glands is very limited. Protein expression profiling of normal pituitary tissue may lead to discovery of novel proteins playing an important role in the physiology of pituitary glands and can lead to better understanding of pituitary gland diseases. We aimed to carry out systematic proteomic profiling of adenohypophysis from human pituitary glands using high-resolution Fourier transform mass spectrometer. A total of 2,175 proteins were identified in this study of which, 105 proteins were identified for the first time as compared to high throughput proteomic-based studies from human pituitary glands. The comprehensive list of proteins identified in this study will facilitate the better understanding the role of this important gland in health and disease.
2019-01-02 | PXD005819 | Pride
Project description:The purpose of this research is to determine whether the drug, Bevacizumab (a monoclonal anti VEGF-A antibody), which is approved to treat patients with metastatic colon cancer induces hyperprolactinemia (increased prolactin secretion) in humans with intact pituitary function. Past studies have shown Bevacizumab to shrink tumor size and also increase prolactin levels. The mechanism of the hyperprolactinemia might be inhibition of pituitary portal vein transport, suggesting that Bevacizumab induces prolactin secretion from normal lactotrophs in the pituitary gland.
Patients who have been treated with Bevacizumab for at least one month will be recruited to participate.
The subjects who are being treated with Bevacizumab by Dr. Stephen Wolin (a sub-investigator) will be screened by him for study eligibility. Dr. Wolin will approach eligible patients with all the information and background of the study and see if they have an interest in being consented.
If consented, there will be 2 blood draws for the research that is not part of their standard care in which 10 ml of blood is collected and prolactin, growth hormone, IGF-I, TSH, thyroxine, ACTH, and cortisol will be measured. One 5ml blood draw will occur before the administration of Bevacizumab and the second 5 ml blood draw will occur after the administration of the Bevacizumab. The investigators will then review the laboratory results. The blood tests are of the hormones of the pituitary gland to test pituitary function and see if there are any abnormalities with the secretions of the gland. Pituitary function abnormalities and hyperprolactinemia are diagnosed by looking at hormone levels in the blood and comparing them to the normal reference ranges.
This study will only involve 10 subjects and will be conducted entirely at Cedars-Sinai Medical Center.
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Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor. Examination of 3 transcriptional regulators in mouse liver
2014-01-07 | E-GEOD-53828 | biostudies-arrayexpress
Project description:Overproduction of adrenal hormones causes obesity and hypertension, whereas adrenalectomy (ADX) leads to weight loss and hypotension. The pituitary gland is a major target organ for the adrenal hormones. To identify potential mediators for the effect of ADX on pituitary system regulating weight loss and hypotension, we investigated the effect of ADX on pituitary gene expression using serial analysis of gene expression (SAGE). The numbers of analyzed SAGE tag were 126688 tags for intact mice (n = 51) and 59482 tags for ADX mice (n = 12), which corresponded to 45151 and 21790 distinct tag species, respectively. Thirty-three pituitary genes were differentially expressed between intact and ADX mice. Three genes encoding for pro-opiomelanocortin have been upregulated by ADX. The ADX has induced the gene expression of growth hormone while downregulating an expressed sequence tag similar to (EST) growth hormone. The ADX reduced the expression of genes involved in mitochondrial oxidative phosphorylation, such as NADH dehydrogenase 3 and cytochrome c oxidase 3, whereas neuromedin B gene were dramatically induced. In addition, the ADX increased the expression levels of other three genes involved in hormone release (response to metastatic cancers 1), extracellular matrix (matrix gamma-carboxyglutamate gla protein), and cation transport (solute carrier family member 17). Moreover, one functionally-uncharacterized and 20 novel transcripts were significantly modulated by ADX. Thus the current study has revealed the alterations in the pituitary gene expression that may play key roles in the mechanisms of ADX-induced weight loss and hypotension. Keywords: adrenalectomy, serial analysis of gene expression Rodents and pituitary gland sampling. Male C57BL6 mice were obtained from Charles River Laboratories (St. Constant, QC, Canada), at 12-14 weeks of age. Mice were housed in an air-conditioned room (19-25?) with controlled lighting from 07:15 to 19:15 h and were given free access to food (Lab Rodent Diet No. 5002) and water. One week prior to sampling of pituitary gland, adrenalectomy was performed in mice of ADX groups (n = 12). The ADX mice received sodium chloride (0.9g/dl) in their drinking water after the surgery. All mice were killed between 08:30 and 12:30 by decapitation under isoflurane anesthesia. Brain was removed from the skull and the pituitary gland was immediately dissected. The pituitary gland was immediately frozen in liquid nitrogen, pooled together for each group, and stored at -80? until RNA extraction.
2007-12-18 | E-GEOD-5879 | biostudies-arrayexpress
Project description:To elucidate how the core circadian component BMAL1 and clock regulate the osteogenic capacity of human bone marrow MSCs, RNA-seq was performed to study the impact of diminishing core component BMAL1 or CLOCK in MSCs by lentiviruses.
2022-07-26 | GSE208729 | GEO
Project description:The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. RNAseq was performed on peritoneal macrophages from wild type and BMAL1 knock out mice.
2019-12-20 | E-MTAB-8411 | biostudies-arrayexpress