Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. Overall design: RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.
Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.
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View SamplesOur goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View SamplesOur goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Treatment
View SamplesOur goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part
View SamplesTwo patients with alopecia areata were treated with systemic ruxolitinib. Skin biopsies were taken before starting treatment and 12 weeks after starting treatment.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part, Disease, Treatment
View SamplesOur goal was to develop a transcriptomic description of affected alopecic skin from aged C3H/HeJ mice. Affected skin from 3 mice was compared to skin from similarly aged but unaffected C3H/HeJ mice.
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Specimen part
View SamplesThe human C-type lectin Reg3a (HIP/PAP) is an antimicrobial peptide that kills Gram-positive bacteria. Reg3a preserves gut microbiota homeostasis, reinforces intestinal barrier function and thereby helps to fight induced colitis in mice.
Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis.
Specimen part, Treatment
View SamplesBy gating cell cycle progression to specific times of the day, the intracellular circadian clock is thought to reduce the exposure of replicating cells to potentially hazardous environmental and endogenous genotoxic compounds. Although core clock gene defects that eradicate circadian rhythmicity can cause an altered in vivo genotoxic stress response and aberrant proliferation rate, it remains to be determined to what extent these cell-cycle-related phenotypes are due to a cell-autonomous lack of circadian oscillations. We investigated the DNA damage sensitivity and proliferative capacity of cultured primary Cry1-/-|Cry2-/- fibroblasts. Contrasting previous in vivo studies, we show that the absence of CRY proteins does not affect the cell-autonomous DNA damage response upon exposure of primary cells in vitro to genotoxic agents, but causes cells to proliferate faster. By comparing primary wild type, Cry1-/-|Cry2-/-, Cry1+/-|Cry2-/- and Cry1-/-|Cry2+/- fibroblasts, we provide evidence that CRY proteins influence cell cycle progression in a cell-autonomous, but circadian clock-independent manner and that the accelerated cell cycle progression of Cry-deficient cells is caused by global dysregulation of Bmal1-dependent gene expression. These results suggest that the inconsistency between in vivo and in vitro observations might be attributed to systemic circadian control rather than a direct cell-autonomous control.
Mammalian cryptochromes impinge on cell cycle progression in a circadian clock-independent manner.
Specimen part
View SamplesRegulation of homeostasis and development of cardiac muscle tissues is controlled by a core set of transcription factors. The MEF2 family plays a critical role in these processes.
Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
Specimen part, Disease
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