Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression.
dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.
Cell line
View SamplesAnalysis of primary bovine aortic endothelial cells treated for 24 hours with TGF-beta 1 5 ng/ml. TGF-beta 1 has been shown to induce endothelial-to-mesenchymal transition (EndoMT) and to be implicated in differentiation of endothelial cells into smooth muscle-like cells as occurred in vascular neointimal formation.
LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling.
Specimen part
View SamplesDominant gain-of-function alleles of Arabidopsis phytochrome B were recently shown to confer light-independent, constitutive photomorphogenic (cop) phenotypes to transgenic plants (Su & Lagarias 2007 Plant Cell 19, 2124-2139). In the present study, comparative transcript profiling experiments were performed to assess whether the pattern of gene expression regulated by these alleles accurately reflects the process of photomorphogenesis in wild-type Arabidopsis. Whole genome transcriptional profiles of dark-grown phyAphyB seedlings expressing the Y276H mutant of phyB (YHB) revealed that YHB reprograms about 13% of the Arabidopsis transcriptome in a light-independent manner. The YHB-regulated transcriptome proved qualitatively similar to, but quantitatively greater than those of wild-type seedlings grown under 15 or 50 umol m-2 m-1 continuous red light (Rc). Among the 2977 genes statistically significant two-fold (SSTF) regulated by YHB in the absence of light include those encoding components of the photosynthetic apparatus, tetrapyrrole/pigment biosynthetic pathways and early light-responsive signaling factors. Approximately 80% of genes SSTF regulated by Rc were also YHB-modulated. Expression of a notable subset of 346 YHB-regulated genes proved to be strongly attenuated by Rc, indicating compensating regulation by phyC-E and/or other Rc-dependent processes. Since the majority of these 346 genes are regulated by the circadian clock, these results suggest that phyA- and phyB-independent light signaling pathway(s) strongly influence clock output. Together with the unique plastid morphology of dark-grown YHB seedlings, these analyses indicate that the YHB mutant induces constitutive photomorphogenesis via faithful reconstruction of phyB signaling pathways in a light-independent fashion.
A light-independent allele of phytochrome B faithfully recapitulates photomorphogenic transcriptional networks.
No sample metadata fields
View SamplesEndothelin-1 (ET-1) plays a critical role in connective tissue remodeling by fibroblasts during tissue repair and fibrosis. We investigated the molecular pathways in the transmission of ET-1 signals that lead to features of connective tissue remodeling, in particular the role of FAK (focal adhesion kinase).
Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation.
Specimen part, Treatment
View SamplesThe intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases.
Distinct human stem cell populations in small and large intestine.
Specimen part
View SamplesColorectal cancer is one of the most common cancers in the world. Histological staging is efficient but combination with molecular markers may improve tumors classification. Gene expression profiles have been defined as prognosis predictors among stage II and III tumors but their implementation in medical practice remains controversial. Stage-II tumors have been recognized as a heterogeneous group and high-risk morphologic features have been retained as justifying adjuvant chemotherapy. We propose here the investigation of clinical features and expression profiles from stage II and stage III colon carcinomas without DNA mismatch repair defect. A series of 130 colon cancer samples was retained. Expression profiles were established on oligonucleotide microarrays and processed in the R/Bioconductor environment. Hierarchical then supervised analyses were successively performed applying the data-sampling approach. A molecular signature of seven genes was found to cluster stage III tumors with an adjusted p-values lower than 10^-10. A subgroup of stage-II tumors aggregated this cluster in both series. No correlation was found between with the disease severity but the function of the discriminating genes suggests that tumors have been classified according to their putative response to adjuvant targeted or classic therapies. Further pharmacogenetic studies might document this observation.
A seven-gene signature aggregates a subgroup of stage II colon cancers with stage III.
Sex, Age, Specimen part
View SamplesAnalysis of expression profiles in stage II colon cancer according to the APC gene status
Expression Profiles in Stage II Colon Cancer According to APC Gene Status.
Sex, Age, Specimen part
View SamplesDifferentially expressed genes between 171 human soft tissue sarcomas with complex genomics
From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas.
Sex, Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA sequencing validation of the Complexity INdex in SARComas prognostic signature.
Time
View SamplesWe validated the technological and material transfers of the CINSARC signature.
RNA sequencing validation of the Complexity INdex in SARComas prognostic signature.
Time
View Samples