An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,918 protein-coding promoters and 17,918 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing. Overall design: Capped nuclear RNA-seq of wild-type and glp-1 was performed to monitor transcription elongation across C. elegans development and ageing. Two biological replicates were done for each time point (six developmental stages and five ageing timepoints).
Chromatin accessibility dynamics across <i>C. elegans</i> development and ageing.
Cell line, Subject
View SamplesTranslation is a critical cellular process to synthesize proteins from their transcripts. However, translational regulation in antigen-specific T cells in vivo has not been well defined.
Translation is actively regulated during the differentiation of CD8<sup>+</sup> effector T cells.
Sex, Specimen part
View SamplesTranscriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome
Transcriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing.
Specimen part
View SamplesPRDM16 is a strong activator of brown fat-specific genes, while also a repressor of white fat and muscle-specific genes. We asked what other pathways are regulated by PRDM16 in adipocytes that may be critical for brown and/or beige adipogenesis. Using microarray, we found PRDM16 also represses type I Interferon-stimulated genes (ISGs) in adipocytes.
PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfr+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfra+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. Overall design: Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Myf5-CrE;mTmG embryos, were further fractionated based on the expression of PDGFRa, Itga7 and Myf5-cre (GFP). Total mRNA profiles from Myf5-cre(GFP)+PDGFRa+ and Myf5-cre(GFP)+PDGFRa-Itga7+ cells were generated by deep sequenceing
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
No sample metadata fields
View SamplesProtein 4.1B is a 4.1/ezrin/radixin/moesin (FERM) domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers and breast carcinomas. However, its potential tumor suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Downregulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. As expression of Protein 4.1B is frequently downregulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.
Protein 4.1B suppresses prostate cancer progression and metastasis.
No sample metadata fields
View SamplesIn this dataset, we report the gene expression of adjacent Gleason 3 and Gleason 4 foci microdissected from the same prostate cancer sample.
Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4.
No sample metadata fields
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