Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development, function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has been primarily known as a transcriptional activator inducing prostate-specific gene expression. Through integrative analysis of genome-wide AR occupancy and androgen-regulated gene expression, here we report AR as a globally acting transcriptional repressor. This repression is mediated by androgen responsive elements (ARE) and dictated by Polycomb group protein EZH2 and repressive chromatin remodeling. In embryonic stem cells, AR-repressed genes are occupied by EZH2 and harbor bivalent H3K4me3 and H3K27me3 modifications that are characteristic of differentiation regulators, the silencing of which maintains the undifferentiated state. Concordantly, these genes are silenced in castration-resistant prostate cancer rendering a stem cell-like lack of differentiation and tumor progression. Collectively, our data reveal an unexpected role of AR as a transcriptional repressor inhibiting non-prostatic differentiation and, upon excessive signaling, resulting in cancerous de-differentiation. It provides an innovative mechanism for castration resistance and highlights novel therapeutic strategies to treat advanced prostate cancer.
Cooperation between Polycomb and androgen receptor during oncogenic transformation.
Cell line, Treatment
View SamplesHsa-mir-365-2 is one of the two precursors that give rise to miR-365. We discovered that miR-365 directly regulates a lung cancer and developmental gene termed thyroid transcription factor 1 (TTF-1 or NKX2-1).
MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.
Cell line
View SamplesNitrogen and light are two major regulators of plant metabolism and development. While genes involved in the control of each of these signals have begun to be identified, regulators that integrate gene responses to nitrogen and light signals have yet to be determined.
Modeling the global effect of the basic-leucine zipper transcription factor 1 (bZIP1) on nitrogen and light regulation in Arabidopsis.
Specimen part
View SamplesWe stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.
Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines.
Sex, Race
View SamplesAnopheles gambiae,the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis ofA. gambiaehead and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.
Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.
Sex, Specimen part
View SamplesAging within the human hematopoietic system associates with increased incidence of anemia and myeloid neoplasms, decreased bone marrow (BM) cellularity and reduced adaptive immune responses. Similar phenotypes have been observed in mice and shown, at least in part, to involve hematopoietic stem cells (HSCs). However, evidence supporting such an association within human hematopoiesis is still sparse and prompted us to detail characteristics of human hematopoietic stem and progenitor cells throughout ontogeny.
Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias.
Specimen part
View SamplesTo identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate. Results: Exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression and both high and low levels of folate produced additional significant changes in gene expression. Conclusions: A mechanism where TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and non-protective of the developing embryo.
Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure.
Specimen part
View SamplesIn this study, we determined the expression profiles of Pho4 and Cbf1 targeted genes in phosphate perturbation.
Differential binding of the related transcription factors Pho4 and Cbf1 can tune the sensitivity of promoters to different levels of an induction signal.
No sample metadata fields
View SamplesArabidopsis is a non-host to the biotrophic fungus Blumeria graminis f.sp. hordei (Bgh), effectively hindering Bgh ingress to the epidermal cells by deposition of callosic papillae formations, i.e. penetration resistance. To better understand the transcriptional changes in Arabidopsis towards Bgh, we compared un-inoculated and inoculated wild-type Arabidopsis samples, with those an ATAF1 mutant allele, compromised in penetration resistance. The experiment included sampling of 8 rosettes for each replicate sample from 6-weeks old plants, 12 hrs after inoculation. A total of 12 biolocigal replicates were sampled with three replicates from each of the four blocks (Wild-type, ataf1-1, Bgh, control). ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Michael Krogh Jensen. The equivalent experiment is AT31 at PLEXdb.]
Transcriptional regulation by an NAC (NAM-ATAF1,2-CUC2) transcription factor attenuates ABA signalling for efficient basal defence towards Blumeria graminis f. sp. hordei in Arabidopsis.
No sample metadata fields
View SamplesJournal : Blood. 2009 Jul 9;114(2):469-77. Epub 2009 May 13.
Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis.
Specimen part
View Samples