Activator (genetics)

Abstract: Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

Abstract: We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

Abstract: A specific protein, bound to DNA, can activate transcription of a wide array of genes in many eukaryotes. Further analysis suggests a general outline for how eukaryotic transcriptional activators function and are controlled.

Abstract: Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome Loss of function as well as increased dosage of the MECP2 gene cause a host of neuropsychiatric disorders To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2 In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (∼85%) appeared to be activated by MeCP2 We selected six genes and confirmed that MeCP2 binds to their promoters Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription