RNA from wt and SIN1 knock-out MEF cell lines were compared
mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.
Specimen part
View SamplesMost tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila.
Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
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View SamplesWnt9b is expressed in the ureteric bud of the kidney at all stages of development. The Wnt9b cneo allele functions as a partial loss of function. Wnt9bcneo/cneo mutant kidneys initially develop normally but exhaust their nephron progenitor cells by E15.5. Here, we have compared expression between Wnt9bcneo/+ and Wnt9bcneo/cneo kidneys. Additional urogenital tissue (adrenal glands, reproductive tracts and bladder) may have been included in some samples.
No associated publication
Specimen part
View SamplesWnt9b is expressed in the ureteric bud of the kidney at all stages of development. In Wnt9b mutants, the ureteric bud forms but the metanephric mesenchyme is never induced to undergo differentiation.
Myc cooperates with β-catenin to drive gene expression in nephron progenitor cells.
Specimen part
View SamplesEfferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Specimen part
View SamplesThe significant changes of hematopoietic cells induced by Xbp1S expression indicate that there is global alteration in gene expression. UPR induces transcription of Xbp1, and phosphorylation of the ER transmembrane kinase IRE1 initiates UPR-mediated mRNA splicing of Xbp1, resulting in the production of Xbp1S, an active form of a basic leucine zipper transcription factor. In the present study, Xbp1S retrovirus vector infected 32cl3 cells show cell cycle arrest and myeloid differentiation. Xbp1S may modulate important genes of differentiation and the cell cycle.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Specimen part
View SamplesCell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Specimen part, Cell line
View SamplesWe conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.
No associated publication
Specimen part
View SamplesWe established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi
No associated publication
Specimen part
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