Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct ionic stress sensing and mitigation by the transcription factor NFAT5

ABSTRACT: Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. To investigate the composition of NFAT5 condensates in response to hypertonic stress, proteins in close proximity of NFAT5 were identified using a variant of NFAT5 fused to TurboID as bait. Hypertonic stress increases NFAT5 proximity to protein complexes belonging to the GO gene sets of “transcription coactivator activity” and “positive regulation of DNA templated transcription initiation.” Closer inspection revealed that the association between NFAT5 and two transcriptional co-activators (the mediator complex and BRD4) and RNAPII itself increased in response to hypertonic stress.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Frederic Lamoliatte

LAB HEAD: Rajat Rohatgi

PROVIDER: PXD052591 | Pride | 2025-04-17

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20210908_FL_Chandni_DA_3T3_01.raw	Raw
	20210908_FL_Chandni_DA_3T3_02.raw	Raw
	20210908_FL_Chandni_DA_3T3_03.raw	Raw
	20210908_FL_Chandni_DA_3T3_04.raw	Raw
	20210908_FL_Chandni_DA_3T3_05.raw	Raw

Items per page:

1 - 5 of 49

Similar Datasets

Murine Spleen: Wild type vs Brx haploinsufficiency

Project description:Comaprison of the gene expression profiles of the spleen between wild type and Brx haploinsuffieint mice Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor that regulates hyperosmolarity-responsive genes and helps activated T lymphocytes adapt to and discharge their functions in hyperosmolar environments. We report here that the Rho-type guanine nucleotide exchange factor (GEF) Brx is essential for increased NFAT5 expression in response to osmotic stress in lymphoid tissues. Indeed, brx haploinsufficient mice expressed significantly less NFAT5 in their spleens than wild type controls and their splenocytes had a defective response to osmotic stress in vitro. Haploinsufficient mice also had smaller-sized spleens containing fewer splenocytes, as well as a defective immunoglobulin response to ovalbumin compared to wild type mice. The Brx GEF domain and the p38 mitogen-activated kinase (MAPK) cascade were both required for osmotic stress-mediated induction of NFAT5 in Jurkat cells. Brx physically interacted with the cJun kinase (JNK)-interacting protein (JIP) 4, a scaffold protein for activation of the p38 MAPK cascade that was required for osmotic stress-induced NFAT5 expression. Thus, Brx is a signal integrator for the adaptive response to osmotic stress in the immune system, activating small G proteins, attracting JIP4 and stimulating p38 MAPK, ultimately increasing the expression of NFAT5 and activating hyperosmolarity protective genes, a phenomenon crucial for proper immune function in hyperosmolar environments, such as inflammatory sites and immune organs. Keywords: Genetic modification Two-condition experiment: Wild type and Brx haploinsuffient, 3 replicates, labeling swap for each

2009-02-09 | E-GEOD-10117 | biostudies-arrayexpress

Murine Spleen: Wild type vs Brx haploinsufficiency

2009-02-09 | GSE10117 | GEO

Monitoring Burma mangrove transcriptome changes in response to salt and osmotic stress.

Project description:Generally, salt stress causes both osmotic and ionic stress. To discern the effects of osmotic and ionic specific effects on Burma mangrove transcriptome, we conducted expression profiling in 500 mM NaCl or 1M solbitol treated leaves. This study will lead to a rapid and effective selection of gene that confers high salt tolerance in transgenic plants and to a comprehensive understanding of plant stress response. Keywords: Stress response

2007-03-10 | GSE7228 | GEO

Segment specific loss of NFAT5 function in the kidneys

Project description:Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to osmotic gradient that is generated between renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.3-Cre and Aqp2-Cre) to generate tubule segment and even cell type specific NFAT5 deficient mice in the principal cells of the collecting duct (CD) and in the distal nephron starting in the TAL up to the CD and performed extensive gene expression profiling. In both Nfat5 knockout models, we observed massive changes in gene expression pattern, with heightened inflammatory responses and renal injury, culminating in renal fibrosis. Interestingly, inflammatory responses and fibrosis were much more prominent in the Aqp2Cre+/-Nfat5fl/fl mice that lack NFAT5 only in the collecting duct. By analyzing gene expression in the medullary and cortical regions of the kidney separately, we confirmed that the loss of NFAT5 results in kidney injury that extends beyond hypertonic areas. The correlation between the levels of inflammatory response, injury severity, and fibrosis indicates that cytokines are key mediators of stress signals in the kidney. Thus, NFAT5 is essential not only for adapting to osmotic stress but also for regulating cytokine signaling.

2025-02-05 | GSE276474 | GEO

Genetic ablation of TonEBP/NFAT5 in smooth muscle cells inhibits arterial remodeling

Project description:Chronic biomechanical stress elicits remodeling of the arterial wall and causes detrimental arterial stenosis and stiffening. In this context, molecular determinants controlling proliferation and stress responses of vascular smooth muscle cells (VSMCs) have been insufficiently studied. We identified the transcription factor ‘nuclear factor of activated T-cells 5’ (NFAT5) as crucial regulatory element of mechanical stress responses of VSMCs. The relevance of this observation for biomechanically induced arterial remodeling was investigated in mice upon SMC-specific knockdown of NFAT5. While blood pressure levels, vascular architecture and flow-induced collateral growth were not affected in these mice, both hypertension-mediated arterial thickening and muscularization of pulmonary arteries during pulmonary artery hypertension (PAH) were impaired. In all models, a decrease in VSMC proliferation was observed indicating that NFAT5 controls activation of VSMCs in the remodeling arterial wall. Mechanistically, mechanoactivation of VSMCs promotes nuclear translocation NFTA5c upon its phosphorylation at Y143 and dephosphorylation at S1197. As evidenced by transcriptome studies, loss of NFAT5 in mechanoactivated VSMCs impairs expression of gene products controlling cell cycle and transcription/translation. These findings identify NFAT5 as molecular determinant of VSMC responses to biomechanical stress and arterial thickening.

2018-08-10 | GSE106274 | GEO

Buffer composition affects ribosome footprint precision in Arabidopsis root and shoot

Project description:The goal of this study is to test ionic strength and buffering capacity in polysome extraction buffer on ribosome footprints in Arabidopsis root and shoot.

2016-11-04 | GSE81295 | GEO

Murine keratinocytes NFAT5 knockout secretome LC-MS/MS

Project description:The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most frequent epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. We studied in KCs the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress. Cultured KCs from adult mice secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous components of ‘Epidermal Differentiation Complex’ (EDC), as proline-rich Sprr and S100 proteins. NFAT5 and Mmp3 are co-expressed in basal KCs from fetal and adult skin but not in skin of newborn mice. This is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of newborn mice and suggests, along with the fragile epidermis of adult Nfat5-/- mice, a suppressive effect of NFAT5 on the expression of matrix proteases in skin. Our data suggest that NFAT5 controls the expression of matrix proteases in skin and contributes to the many fold changes during embryonal skin development and skin integrity in adults.

2021-11-16 | PXD028675 | Pride

Engineering a superactivator of smooth muscle gene expression with the Myocardin condensate forming region [RNA-seq]

Project description:Differentiation of smooth muscle cells (SMCs) is accompanied by the expression of a battery of genes controlled by serum response factor (SRF), a ubiquitous transcription factor with weak intrinsic transcriptional activity. Myocardin (MYOCD) is a potent transcriptional coactivator that activates smooth muscle differentiation through its association with SRF. MYOCD forms condensates through its highly disordered transcription activation domain (TAD), whereas SRF displays a diffuse distribution within the nucleus. SRF is recruited to nuclear condensates by the TAD of MYOCD (MYOCD-TAD), thereby triggering the smooth muscle gene program. Swapping the weak TAD of SRF with that of MYOCD enables SRF to form condensates and acquire the ability to reprogram fibroblasts to SMCs. SRF-MYOCD-TAD chimeric protein exhibits stronger transcriptional activity on smooth muscle genes than MYOCD. Using protein proximity labelling, quantitative proteomics and super-resolution confocal microscopy, we show that MYOCD-TAD condensates aggregate chromatin remodelers, RNA polymerases, and mRNA processing factors to drive smooth muscle gene expression. These findings provide insights into the mechanisms whereby nuclear condensates promote tissue-specific gene expression and point toward a strategy for engineering superactivators leveraging transcriptional condensates.

2025-09-02 | GSE294914 | GEO

Engineering a superactivator of smooth muscle gene expression with the Myocardin condensate forming region [ChIP-seq]

2025-09-02 | GSE294913 | GEO

Impact of Nfat5 on normoxia- and hypoxia-exposed mouse lung endothelial cells

Project description:Chronic hypoxia causes detrimental structural alterations in the lung, which are partially dependent on stress responses of the endothelium. In this context, we revealed that hypoxia-exposed murine lung endothelial cells (MLEC) activate nuclear factor of activated T-cells 5 (NFAT5/TonEBP) - a transcription factor that adjusts the cellular transcriptome to cope with multiple environmental stressors. Here, we studied the impact of NFAT5 on hypoxia-induced gene expression in MLEC by comparing the transcriptome of control and Nfat5-deficient MLEC, which were isolated from mouse lungs after exposure to normoxia and hypoxia for 7 days and processed for scRNA seq.

2024-08-08 | GSE255681 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data