Topic
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.
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TL;DR: An RNase protection assay is used that can distinguish between H19 alleles in four subspecies of Mus, to demonstrate that the H19 gene is parentally imprinted, with the active copy derived from the mother.
Abstract: THE mouse H19 gene encodes one of the most abundant RNAs in the developing mouse embryo It is expressed at the blastocyst stage of development, and accumulates to high levels in tissues of endodermal and mesodermal origin (H Kim, unpublished result) After birth the gene is expressed in all tissues except skeletal muscle It lacks a common open reading frame in the 25-kilobase RNA, but has considerable nucleotide sequence similarity between the genes of rodents and humans Expression of the gene in transgenic mice results in late prenatal lethality, suggesting that the dosage of its gene product is strictly controlled The H19 gene maps to the distal segment of mouse chromosome 7, in a region that is parentally imprinted, a process by which genes are differentially expressed on the maternal and paternal chromosomes We have now used an RNase protection assay that can distinguish between H19 alleles in four subspecies of Mus, to demonstrate that the H19 gene is parentally imprinted, with the active copy derived from the mother This assay will be of general use in assaying allele-specific gene expression
1,154 citations
TL;DR: It is found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly, which can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones.
Abstract: The quantitative relation between transcription factor concentrations and the rate of protein production from downstream genes is central to the function of genetic networks. Here we show that this relation, which we call the gene regulation function (GRF), fluctuates dynamically in individual living cells, thereby limiting the accuracy with which transcriptional genetic circuits can transfer signals. Using fluorescent reporter genes and fusion proteins, we characterized the bacteriophage lambda promoter P_R in Escherichia coli. A novel technique based on binomial errors in protein partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly. Thus, biochemical parameters, noise, and slowly varying cellular states together determine the effective single-cell GRF. These results can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones.
1,152 citations
TL;DR: A clinically relevant ATP site inhibitor of mTOR, INK128, is developed, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure.
Abstract: The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted.
1,151 citations
TL;DR: The structure of the H SP-70 family (HSP-70s), regulation of HSP- 70 gene expression, their cytoprotective effects, and the possibility of regulating HSP -70 expression through modulation of signal transduction pathways are focused on.
1,151 citations
TL;DR: It is concluded that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.
Abstract: Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide in single cells are lacking. Here, we present global analyses of allelic expression across individual cells of mouse preimplantation embryos of mixed background (CAST/EiJ × C57BL/6J). We discovered abundant (12 to 24%) monoallelic expression of autosomal genes and that expression of the two alleles occurs independently. The monoallelic expression appeared random and dynamic because there was considerable variation among closely related embryonic cells. Similar patterns of monoallelic expression were observed in mature cells. Our allelic expression analysis also demonstrates the de novo inactivation of the paternal X chromosome. We conclude that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.
1,149 citations