Topic
Transcription factor
About: Transcription factor is a research topic. Over the lifetime, 82881 publications have been published within this topic receiving 5400448 citations. The topic is also known as: transcription factors.
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TL;DR: The transition from the juvenile to the adult phase of shoot development in plants is accompanied by changes in vegetative morphology and an increase in reproductive potential, and the regulatory mechanism is described, which is mediated by sequentially operating miRNAs.
1,344 citations
TL;DR: It is shown, with the use of mice lacking IKK-β in different cell types, that NF-κB is a critical transcriptional activator of HIF-1α and that basal NF-σB activity is required for Hif-1 α protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals.
Abstract: The hypoxic response is an ancient stress response triggered by low ambient oxygen (O2) (ref. 1) and controlled by hypoxia-inducible transcription factor-1 (HIF-1), whose alpha subunit is rapidly degraded under normoxia but stabilized when O2-dependent prolyl hydroxylases (PHDs) that target its O2-dependent degradation domain are inhibited. Thus, the amount of HIF-1alpha, which controls genes involved in energy metabolism and angiogenesis, is regulated post-translationally. Another ancient stress response is the innate immune response, regulated by several transcription factors, among which NF-kappaB plays a central role. NF-kappaB activation is controlled by IkappaB kinases (IKK), mainly IKK-beta, needed for phosphorylation-induced degradation of IkappaB inhibitors in response to infection and inflammation. IKK-beta is modestly activated in hypoxic cell cultures when PHDs that attenuate its activation are inhibited. However, defining the relationship between NF-kappaB and HIF-1alpha has proven elusive. Using in vitro systems, it was reported that HIF-1alpha activates NF-kappaB, that NF-kappaB controls HIF-1alpha transcription and that HIF-1alpha activation may be concurrent with inhibition of NF-kappaB. Here we show, with the use of mice lacking IKK-beta in different cell types, that NF-kappaB is a critical transcriptional activator of HIF-1alpha and that basal NF-kappaB activity is required for HIF-1alpha protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals. IKK-beta deficiency results in defective induction of HIF-1alpha target genes including vascular endothelial growth factor. IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation.
1,340 citations
TL;DR: All estrogen receptor and RNA polymerase II binding sites are mapped on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells, and distinct temporal mechanisms of estrogen-mediated gene regulation are demonstrated.
Abstract: The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation, particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer.
1,340 citations
TL;DR: The switching on and off of Nrf2 protects cells against free radical damage, prevents apoptosis, and promotes cell survival, and is a mechanism of critical importance for cellular protection and cell survival.
1,336 citations
TL;DR: It is shown that disruption of the murine GSK-3β gene results in embryonic lethality caused by severe liver degeneration during mid-gestation, a phenotype consistent with excessive tumour necrosis factor (TNF) toxicity, as observed in mice lacking genes involved in the activation of the transcription factor activation NF-κB.
Abstract: Glycogen synthase kinase-3 (GSK-3)-α and -β are closely related protein-serine kinases, which act as inhibitory components of Wnt signalling during embryonic development and cell proliferation in adult tissues1,2. Insight into the physiological function of GSK-3 has emerged from genetic analysis in Drosophila3,4, Dictyostelium 5 and yeast6,7. Here we show that disruption of the murine GSK-3β gene results in embryonic lethality caused by severe liver degeneration during mid-gestation, a phenotype consistent with excessive tumour necrosis factor (TNF) toxicity, as observed in mice lacking genes involved in the activation of the transcription factor activation NF-κB. GSK-3β-deficient embryos were rescued by inhibition of TNF using an anti-TNF-α antibody. Fibroblasts from GSK-3β-deficient embryos were hypersensitive to TNF-α and showed reduced NF-κB function. Lithium treatment (which inhibits GSK-3; refs 8, 9) sensitized wild-type fibroblasts to TNF and inhibited transactivation of NF-κB. The early steps leading to NF-κB activation (degradation of I-κB and translocation of NF-κB to the nucleus) were unaffected by the loss of GSK-3β, indicating that NF-κB is regulated by GSK-3β at the level of the transcriptional complex. Thus, GSK-3β facilitates NF-κB function.
1,335 citations