The LEF/TCF family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific HMG box that binds Wnt Response Elements (WREs). The E tail isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces a p21-dependent stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not induce p21 or stall cell growth. Microarray analysis revealed that induction of p21 by dnTCF1EWT correlated with a decrease in expression of p21 suppressors that act at multiple levels from transcription (SP5, YAP1, RUNX1), to RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence specific DNA binding domain that can make contacts with 5-RCCG-3 elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a WNT/p21 circuit is driven by C-clamp target gene selection.
A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.
Specimen part
View SamplesAtf1 was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Genome wide transcription profiling reveals a major role for the transcription factor Atf1 in regulation of cell division in Schizosaccharomyces pombe.
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View SamplesSpc1/ Spc1K49R was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Genome wide transcription profiling of the effects of overexpression of Spc1 and its kinase dead mutant in Schizosaccharomyces pombe.
No sample metadata fields
View SamplesCD34 positive hematopoietic stem cells were differentiated into erythroid lineage. Next generation sequencing (NGS) of 5hmC affinity pulldown and RNAseq were performed in four time point of different stages of erythroid differentiation. Overall design: 4 RNA-Seq Samples (d0, d3, d7 and d10); 4 affinity-pulldown (d0, d3, d7 and d10), and 4 input samples (d0, d3, d7 and d10).
Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
MGAT1 and Complex N-Glycans Regulate ERK Signaling During Spermatogenesis.
Age, Specimen part
View SamplesLoss of Mgat1 in spermatogonia was investigated in germ cells from 23 day males. Gene expression changes induced by deletion of Mgat1 were determined using the Affymetrix GeneChip Mouse Gene 2.0 ST Array.
MGAT1 and Complex N-Glycans Regulate ERK Signaling During Spermatogenesis.
Age, Specimen part
View SamplesMechanistic insights into MGAT1 loss during spermatogenesis were investigated in germ cells from 22 day males. Gene expression changes induced by deletion of Mgat 1in spermatogonia were determined using the Affymetrix GeneChip Whole Transcript Plus Reagent Kit.
MGAT1 and Complex N-Glycans Regulate ERK Signaling During Spermatogenesis.
Age, Specimen part
View SamplesWe analyzed the global effect of c-Myb knockdown by sequencing the transcriptomes of K-562 cells transfected with control siRNA and si2992 (MYB knockdown), as well as K-562 cells stably expressing TY-tagged wild type c-Myb and c-Myb D152V transfected with si2992 Overall design: Cells were tranfected with siRNA and 24 hours after total RNA was extracted. Three individual experiments were performed. Libraries were prepared and 125-bp paired-end reads were obtained using an Illumina HiSeq 2500 sequencer
A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function.
Specimen part, Cell line, Subject
View SamplesPurpose: The purpose of this experiment is to expand the repertoire of C. elegans edited transcripts and identify the roles of ADR-1 as indirect regulator of editing and ADR-2 as the only active deaminase in vivo. Methods: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline. Results: Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3’ UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2; and mutations within its dsRNA binding domains abolished both binding and editing regulation. Conclusions: ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo and raises the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing by deaminase-independent mechanisms. Overall design: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline.
The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.
Specimen part, Subject
View SamplesThis study identifies miR-198 as a potential inhibitor of keratinocyte migration in skin
'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing.
Specimen part, Time
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