CREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses.
Plasticity is a remarkable feature of the brain, allowing neuronal structure and function to accommodate to patterns of electrical activity. One component of these long-term changes is the activitydriven induction of new gene expression, which is required for both the long-lasting long-term potentiation of synaptic transmission associated with learning and memory, and the activitydependent survival events that help to shape and wire the brain during development. We have characterized molecular mechanisms by which neuronal membrane depolarization and subsequent calcium influx into the cytoplasm lead to the induction of new gene transcription. We have identified three points within this cascade of events where the specificity of genes induced by different types of stimuli can be regulated. By using the induction of the gene that encodes brain-derived neurotrophic factor (BDNF) as a model, we have found that the ability of a calcium influx to induce transcription of this gene is regulated by the route of calcium entry into the cell, by the pattern of phosphorylation induced on the transcription factor cAMP-response element (CRE) binding protein (CREB), and by the complement of active transcription factors recruited to the BDNF promoter. These results refine and expand the working model of activity-induced gene induction in the brain, and help to explain how different types of neuronal stimuli can activate distinct transcriptional responses.
Transcription of the brain-derived neurotrophic factor (BDNF) gene is regulated in a calcium- and neuron-selective manner; however, the mechanisms that underlie this selectivity are not known. We have characterized a new calcium-response element, CaRE1, that is required for activity-dependent transcription of BDNF exon III and have cloned a transcription factor, CaRF, that activates transcription from BDNF promoter III in a CaRE1-dependent manner. The transcriptional activity of CaRF is regulated in a calcium- and neuron-selective manner, suggesting that CaRF may confer selectivity upon the activity-dependent induction of BDNF exon III expression.
As the most abundant internal modification of mRNA, N 6 -methyladenosine (m 6 A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m 6 A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m 6 A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m 6 A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m 6 A-dependent manner. The vir mutant, in which the level of m 6 A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m 6 A methylome in the vir mutant revealed a transcriptomewide loss of m 6 A modification in the 3ʹ untranslated region (3ʹ-UTR). We demonstrated further that VIR-mediated m 6 A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3ʹ-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m 6 A methylation and 3ʹ-UTR length and mRNA stability during stress adaptation.
To identify molecular mechanisms that control activity-dependent gene expression in the CNS, we have characterized the factors that mediate activity-dependent transcription of BDNF promoter III. We report the identification of a Ca(2+)-responsive E-box element, CaRE2, within BDNF promoter III that binds upstream stimulatory factors 1 and 2 (USF1/2) and show that USFs are required for the activation of CaRE2-dependent transcription from BDNF promoter III. We find that the transcriptional activity of the USFs is regulated by Ca(2+)-activated signaling pathways in neurons and that the USFs bind to the promoters of a number of neuronal activity-regulated genes in vivo. These results suggest a new function for the USFs in the regulation of activity-dependent transcription in neurons.
Background Sweet potato ( Ipomoea batatas L.) is the sixth most important food crop in the world. The formation and development of storage roots in sweet potato is a highly complicated and genetically programmed process. However, the underlying mechanisms of storage root development have not yet been elucidated. Results To better understand the molecular mechanisms involved in storage root development, a combined analysis of the transcriptome and proteome of sweet potato fibrous roots (F) and storage roots at four different stages (D1, D3, D5 and D10) was performed in the present study. A total of 26,273 differentially expressed genes were identified in a comparison between the fibrous root library and four storage root libraries, while 2558 proteins showed a 1.0-fold or greater expression difference as indicated by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The combination of the transcriptome and proteome analyses and morphological and physiological data revealed several critical pathways involved in storage root formation and development. First, genes/proteins involved in the development of meristems/cambia and starch biosynthesis were all significantly upregulated in storage roots compared with fibrous roots. Second, multiple phytohormones and the genes related to their biosynthesis showed differential expression between fibrous roots and storage roots. Third, a large number of transcription factors were differentially expressed during storage root initiation and development, which suggests the importance of transcription factor regulation in the development of storage roots. Fourth, inconsistent gene expression was found between the transcriptome and proteome data, which indicated posttranscriptional regulatory activity during the development of storage roots. Conclusion Overall, these results reveal multiple events associated with storage root development and provide new insights into the molecular mechanisms underlying the regulatory networks involved in storage root development. Electronic supplementary material The online version of this article (10.1186/s12870-019-1731-0) contains supplementary material, which is available to authorized users.
The jasmonic acid (JA) pathway plays a key role in plant defense responses against herbivorous insects. CORONATINE INSENSITIVE1 (COI1) is an F-box protein essential for all jasmonate responses. However, the precise defense function of COI1 in monocotyledonous plants, especially in rice (Oryza sativa L.) is largely unknown. We silenced OsCOI1 in rice plants via RNA interference (RNAi) to determine the role of OsCOI1 in rice defense against rice leaf folder (LF) Cnaphalocrocis medinalis, a chewing insect, and brown planthopper (BPH) Nilaparvata lugens, a phloem-feeding insect. In wild-type rice plants (WT), the transcripts of OsCOI1 were strongly and continuously up-regulated by LF infestation and methyl jasmonate (MeJA) treatment, but not by BPH infestation. The abundance of trypsin protease inhibitor (TrypPI), and the enzymatic activities of polyphenol oxidase (PPO) and peroxidase (POD) were enhanced in response to both LF and BPH infestation, but the activity of lipoxygenase (LOX) was only induced by LF. The RNAi lines with repressed expression of OsCOI1 showed reduced resistance against LF, but no change against BPH. Silencing OsCOI1 did not alter LF-induced LOX activity and JA content, but it led to a reduction in the TrypPI content, POD and PPO activity by 62.3%, 48.5% and 27.2%, respectively. In addition, MeJA-induced TrypPI and POD activity were reduced by 57.2% and 48.2% in OsCOI1 RNAi plants. These results suggest that OsCOI1 is an indispensable signaling component, controlling JA-regulated defense against chewing insect (LF) in rice plants, and COI1 is also required for induction of TrypPI, POD and PPO in rice defense response to LF infestation.
Melatonin (MT) is a multifunctional molecule in animals and plants and is involved in defense against salinity stress in various plant species. In this study, MT pretreatment was simultaneously applied to the roots and leaves of sweet potato seedlings [Ipomoea batatas (L.) Lam.], which is an important food and industry crop worldwide, followed by treatment of 150 mM NaCl. The roles of MT in mediating K+/Na+ homeostasis and lipid metabolism in salinized sweet potato were investigated. Exogenous MT enhanced the resistance to NaCl and improved K+/Na+ homeostasis in sweet potato seedlings as indicated by the low reduced K+ content in tissues and low accumulation of Na+ content in the shoot. Electrophysiological experiments revealed that exogenous MT significantly suppressed NaCl-induced K+ efflux in sweet potato roots and mesophyll tissues. Further experiments showed that MT enhanced the plasma membrane (PM) H+–ATPase activity and intracellular adenosine triphosphate (ATP) level in the roots and leaves of salinized sweet potato. Lipidomic profiling revealed that exogenous MT completely prevented salt-induced triacylglycerol (TAG) accumulation in the leaves. In addition, MT upregulated the expression of genes related to TAG breakdown, fatty acid (FA) β-oxidation, and energy turnover. Chemical inhibition of the β-oxidation pathway led to drastic accumulation of lipid droplets in the vegetative tissues of NaCl-stressed sweet potato and simultaneously disrupted the MT-stimulated energy state, PM H+–ATPase activity, and K+/Na+ homeostasis. Results revealed that exogenous MT stimulated TAG breakdown, FA β-oxidation, and energy turnover under salinity conditions, thereby contributing to the maintenance of PM H+–ATPase activity and K+/Na+ homeostasis in sweet potato.
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