Regulated Gene Expression and Controlled Protein Turnover: Partners in Response to Environmental Changes

2007 ◽  
Vol 2 (5) ◽  
pp. 252-252
mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Jeongjoon Choi ◽  
Heeju Kim ◽  
Yoonjee Chang ◽  
Woongjae Yoo ◽  
Dajeong Kim ◽  
...  

ABSTRACTSignal transduction systems dictate various cellular behaviors in response to environmental changes. To operate cellular programs appropriately, organisms have sophisticated regulatory factors to optimize the signal response. The PhoP/PhoQ master virulence regulatory system of the intracellular pathogenSalmonella entericais activated inside acidic macrophage phagosomes. Here we report thatSalmonelladelays the activation of this system inside macrophages using an inhibitory protein, EIIANtr(a component of the nitrogen-metabolic phosphotransferase system). We establish that EIIANtrdirectly restrains PhoP binding to its target promoter, thereby negatively controlling the expression of PhoP-activated genes. PhoP furthers its activation by promoting Lon-mediated degradation of EIIANtrat acidic pH. These results suggest thatSalmonellaensures robust activation of its virulence system by suspending the activation of PhoP until a sufficient level of active PhoP is present to overcome the inhibitory effect of EIIANtr. Our findings reveal how a pathogen precisely and efficiently operates its virulence program during infection.IMPORTANCETo accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogenSalmonellacontrols the timing and level of virulence gene expression by using an inhibitory protein, EIIANtr. A DNA binding master virulence regulator, PhoP, controls various virulence genes inside acidic phagosomes.Salmonelladecreases EIIANtramounts at acidic pH in a Lon- and PhoP-dependent manner. This, in turn, promotes expression of the PhoP-activated virulence program because EIIANtrhampers activation of PhoP-regulated genes by interfering with PhoP binding to DNA. EIIANtrenablesSalmonellato impede the activation of PhoP-regulated gene expression inside macrophages. Our findings suggest thatSalmonellaachieves programmed delay of virulence gene activation by adjusting levels of an inhibitory factor.


2014 ◽  
Author(s):  
Irina Makarevitch ◽  
Amanda J Waters ◽  
Patrick T West ◽  
Michelle C Stitzer ◽  
Jeffrey Ross-Ibarra ◽  
...  

Transposable elements (TEs) account for a large portion of the genome in many eukaryotic species. Despite their reputation as "junk" DNA or genomic parasites deleterious for the host, TEs have complex interactions with host genes and the potential to contribute to regulatory variation in gene expression. It has been hypothesized that TEs and genes they insert near may be transcriptionally activated in response to stress conditions. The maize genome, with many different types of TEs interspersed with genes, provides an ideal system to study the genome-wide influence of TEs on gene regulation. To analyze the magnitude of the TE effect on gene expression response to environmental changes, we profiled gene and TE transcript levels in maize seedlings exposed to a number of abiotic stresses. Many genes exhibit up- or down-regulation in response to these stress conditions. The analysis of TE families inserted within upstream regions of up-regulated genes revealed that between four and nine different TE families are associated with up-regulated gene expression in each of these stress conditions, affecting up to 20% of the genes up-regulated in response to abiotic stress and as many as 33% of genes that are only expressed in response to stress. Expression of many of these same TE families also responds to the same stress conditions. The analysis of the stress- induced transcripts and proximity of the transposon to the gene suggests that these TEs may provide local enhancer activities that stimulate stress-responsive gene expression. Our data on allelic variation for insertions of several of these TEs show strong correlation between the presence of TE insertions and stress-responsive up-regulation of gene expression. Our findings suggest that TEs provide an important source of allelic regulatory variation in gene response to abiotic stress in maize.


2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.


2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.


2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  

[[This is a Stage 1 Registered Report manuscript. The project was submitted for review to eNeuro. Upon revision and acceptance, this version of the manuscript was pre-registered on the OSF (9/11/2019, https://osf.io/fqh8j) (but due to an oversight not posted as a preprint until July 2020). A Stage 2 manuscript is now posted as a pre-print (https://psyarxiv.com/h59jv) and is under review at eNeuro. A link to the final Stage 2 manuscript will be added when available.]]There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting make different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval-failure then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day from training), a forgotten memory (8 days from training), and a savings memory (8 days from training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We find that the transcriptional correlates of savings are [highly similar / somewhat similar / unique] relative to new (1-day-old) memories. Specifically, savings memory and a new memory share [X] of [Y] regulated transcripts, show [strong / moderate / weak] similarity in sets of regulated transcripts, and show [r] correlation in regulated gene expression, which is [substantially / somewhat / not at all] stronger than at forgetting. Overall, our results suggest that forgetting represents [decay / retrieval-failure / mixed mechanisms].


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