The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
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View SamplesTemporal coordination of developmental programs is necessary for normal ontogeny, but the mechanism by which this is accomplished is poorly understood. We have previously shown that two components of the Mediator CDK8 module, CENTER CITY (CCT/MED12) and GRAND CENTRAL (GCT/MED13), are required for timing of pattern formation during embryogenesis in Arabidopsis.
The Arabidopsis Mediator CDK8 module genes CCT (MED12) and GCT (MED13) are global regulators of developmental phase transitions.
Specimen part
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microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesBACKGROUND & AIMS: We performed an integrated analysis to identify microRNAs (miRNAs) and mRNAs with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesA LHX4 transgenic reporter line with high specificity for developing mouse cone photoreceptors was identified and used to purify early stage cone photoreceptors for profiling by single cell RNA sequencing. Overall design: Collection of FACS-sorted LHX4::GFP+ E14.5 early cones and LHX4::GFP- retinal cells for further analysis.
Identification of Genes With Enriched Expression in Early Developing Mouse Cone Photoreceptors.
Specimen part, Cell line, Subject
View SamplesHere we report a transcriptomic analysis of fate-restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate-restricted retinal progenitor cells Overall design: Comparison of two FACS-sorted chick retinal progenitor cell populations after electroporation of reporter plasmids and 20hr culture.
Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells.
Specimen part, Subject
View SamplesHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/�-catenin signaling. Microarray analysis identified two tumor subclasses resembling distinct phases of liver development, and a 16-gene signature discriminated invasive and metastatic hepatoblastomas, and predicted prognosis with high accuracy. <br></br>
Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesChronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with complex pathological features and largely unknown etiologies. Identification and validation of biomarkers for this disease could facilitate earlier diagnosis, appreciation of disease subtypes and/or determination of response to therapeutic intervention. To identify gene expression markers for COPD, we performed genome-wide expression profiling of lung tissue from 56 subjects using the Affymetrix U133 Plus 2.0 array. Lung function measurements from these subjects ranged from normal, un-obstructed to severely obstructed. Analysis of differential expression between cases (FEV1<70%, FEV1/FVC<0.7) and controls (FEV1>80%, FEV1/FVC>0.7) identified a set of 65 probe sets representing discrete markers associated with COPD. Correlation of gene expression with quantitative measures of airflow obstruction (FEV1 or FEV1/FVC) identified a set of 220 probe sets. A total of 31 probe sets were identified that showed evidence of significant correlation with quantitative traits and differential expression between cases and controls.
Molecular biomarkers for quantitative and discrete COPD phenotypes.
Race
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Rapid chromatin repression by Aire provides precise control of immune tolerance.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Specimen part
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