Regulation of gene expression

About: Regulation of gene expression is a research topic. Over the lifetime, 85456 publications have been published within this topic receiving 5832845 citations. The topic is also known as: GO:0010468 & gene expression regulation.

Single-RNA counting reveals alternative modes of gene expression in yeast.

Abstract: Understanding the kinetics of gene expression involves accurate quantitation of gene expression. This is now undertaken by quantifying nascent-RNA levels and relating this indication of transcriptional activity to mRNA abundance in single yeast cells. Combining these measurements with computational modeling indicates that the tested yeast housekeeping genes are probably expressed through single initiation events, whereas a SAGA-transcribed gene shows behavior consistent with transcriptional bursting. Proper execution of transcriptional programs is a key requirement of gene expression regulation, demanding accurate control of timing and amplitude. How precisely the transcription machinery fulfills this task is not known. Using an in situ hybridization approach that detects single mRNA molecules, we measured mRNA abundance and transcriptional activity within single Saccharomyces cerevisiae cells. We found that expression levels for particular genes are higher than initially reported and can vary substantially among cells. However, variability for most constitutively expressed genes is unexpectedly small. Combining single-transcript measurements with computational modeling indicates that low expression variation is achieved by transcribing genes using single transcription-initiation events that are clearly separated in time, rather than by transcriptional bursts. In contrast, PDR5, a gene regulated by the transcription coactivator complex SAGA, is expressed using transcription bursts, resulting in larger variation. These data directly demonstrate the existence of multiple expression modes used to modulate the transcriptome.

GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.

Abstract: Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.

Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells

Abstract: 92-kDa Type IV collagenase, a member of matrix metalloproteinases, is believed to play a critical role in physiological tissue-remodeling processes and also in many pathological conditions such as tumor invasion We analyzed the 5'-flanking sequence of the 92 kDa type IV collagenase gene that controls the expression of the gene by ligating it to the chloramphenicol acetyltransferase gene Deletion and mutation analysis revealed that three motifs, homologous to the binding sites for AP-1, NF-kappa B, and Sp-1 proteins, contributed positively to induction by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF alpha) The AP-1 site was indispensable but not sufficient for the induction and required synergistic cooperation with either the kappa B or the Sp-1 site In OST cells, a nuclear factor which bound to Sp-1 was constitutively expressed, and those bound to AP-1 and kappa B elements were rapidly induced by TNF alpha treatment Comparison of the findings with those for the promoters of other TPA-inducible matrix metalloproteinases, interstitial collagenase and stromelysin 1, revealed that the signal to the AP-1 sites is common for the TPA-inducibility of the genes but that the signals to the kappa B or Sp-1 sites, which are not present in interstitial collagenase and stromelysin 1 promoters, are the unique determinant for the inducibility of the 92 kDa type IV collagenase gene

Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

Abstract: To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.