Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [RNA]

ABSTRACT: Aging changes global transcriptome including protein-coding and noncoding RNAs. Whether aging dependent lncRNAs undergo conserved regulation and function still remain unknown. We report aging dependent lncRNAs carry signature of evolutionary constraint and significantly enriched for targets of transcription factors and RNA binding proteins. Aging dependent lncRNAs is conservatively under NFκB pathway regulation. CRISPR screening for NFκB pathway found that aging dependent lncRNAs also extensively regulate NFκB pathway. The human NFKBMARL-1 is an evolutionary conserved lncRNA that can be traced to 29Mya before human. NFKBMARL-1 is induced during aging, inflammation and senescence through NFκB pathway. Reciprocally, NFKBMARL-1 directly regulates NFKBIZ in cis within same topological associated domain (TAD). NFKBMARL-1 binds to enhancer of NFKBIZ and recruits RELA to the NFKBIZ promoters and participates phase separation. These findings reveal that aging dependent lncRNAs are previously under-appreciated contributors to the evolutionary conservation and regulation of NFκB pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE167507 | GEO | 2021/03/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [ChIRP]

Project description:Aging changes global transcriptome including protein-coding and noncoding RNAs. Whether aging dependent lncRNAs undergo conserved regulation and function still remain unknown. We report aging dependent lncRNAs carry signature of evolutionary constraint and significantly enriched for targets of transcription factors and RNA binding proteins. Aging dependent lncRNAs is conservatively under NFκB pathway regulation. CRISPR screening for NFκB pathway found that aging dependent lncRNAs also extensively regulate NFκB pathway. The human NFKBMARL-1 is an evolutionary conserved lncRNA that can be traced to 29Mya before human. NFKBMARL-1 is induced during aging, inflammation and senescence through NFκB pathway. Reciprocally, NFKBMARL-1 directly regulates NFKBIZ in cis within same topological associated domain (TAD). NFKBMARL-1 binds to enhancer of NFKBIZ and recruits RELA to the NFKBIZ promoters and participates phase separation. These findings reveal that aging dependent lncRNAs are previously under-appreciated contributors to the evolutionary conservation and regulation of NFκB pathway.

2021-03-08 | GSE167504 | GEO

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [CRISPR]

Project description:Aging changes global transcriptome including protein-coding and noncoding RNAs. Whether aging dependent lncRNAs undergo conserved regulation and function still remain unknown. We report aging dependent lncRNAs carry signature of evolutionary constraint and significantly enriched for targets of transcription factors and RNA binding proteins. Aging dependent lncRNAs is conservatively under NFκB pathway regulation. CRISPR screening for NFκB pathway found that aging dependent lncRNAs also extensively regulate NFκB pathway. The human LINC02085 is an evolutionary conserved lncRNA that can be traced to 29Mya before human. LINC02085 is induced during aging, inflammation and senescence through NFκB pathway. Reciprocally, LINC02085 directly regulates NFKBIZ in cis within same topological associated domain (TAD). LINC02085 binds to enhancer of NFKBIZ and recruits RELA to the NFKBIZ promoters and participates phase separation. These findings reveal that aging dependent lncRNAs are previously under-appreciated contributors to the evolutionary conservation and regulation of NFκB pathway.

2021-03-08 | GSE167510 | GEO

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [RNA]

Project description:Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [RNA]

| PRJNA704830 | ENA

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [CRISPR]

Project description:Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [CRISPR]

| PRJNA704832 | ENA

Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [ChIRP]

Project description:Aging-associated lncRNAs carry evolutionary constraints and participate in NFκB signaling [ChIRP]

| PRJNA704835 | ENA

Aging-associated lncRNAs are evolutionarily conserved and participate in NFκB signaling

Project description:Aging-associated lncRNAs are evolutionarily conserved and participate in NFκB signaling

| PRJNA704824 | ENA

IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL (NFKBIZ inhibition)

Project description:Constitutive activation of the nuclear factor-kappa B (NF-kB) pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Recurrent mutations of NF-kB regulators that cause constitutive activity of this oncogenic pathway have been identified. However, it remains unclear how specific target genes are regulated. We identified the IkB-like protein NFKBIZ that binds NF-kB subunits and enhances transactivation of some NF-kB target genes while repressing others, to be upregulated in ACB compared to GCB DLBCL primary patient samples (p=5.1 x 10^-37). Knockdown of NFKBIZ by RNA interference was toxic to ABC but not GCB DLBCL cell lines. Gene expression profiling following NFKBIZ knockdown significantly downregulated a large number of NF-kB target genes, suggesting a central role in regulating NF-kB signaling. To further investigate the molecular mechanisms of how NFKBIZ mediates NF-kB signaling in ABC DLBCL, we performed immunoprecipitations and detected an interaction of NFKBIZ with both p50 and p52 NF-kB subunits, indicating that both the canonical and non-canonical NF-kB pathways are regulated by NFKBIZ. Collectively, our data imply that NFKBIZ is required for NF-kB signaling in ABC DLBCL and thus might represent a promising molecular target for future therapies. The complete dataset is comprised of three experiments with the male HBL-1 ABC DLBCL cell line: a) 8 paired GEP measurements after NFKBIZ inhibition by shRNA, b) 6 paired GEP measurements after applying the MLN inhibitor and c) 4 two-color measurements after applying a MALT inhibitor. This dataset includes 8 paired GEP measurements after NFKBIZ inhibition by shRNA.

2013-07-22 | E-GEOD-46971 | biostudies-arrayexpress

IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL (MLN inhibition)

Project description:Constitutive activation of the nuclear factor-kappa B (NF-kB) pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Recurrent mutations of NF-kB regulators that cause constitutive activity of this oncogenic pathway have been identified. However, it remains unclear how specific target genes are regulated. We identified the IkB-like protein NFKBIZ that binds NF-kB subunits and enhances transactivation of some NF-kB target genes while repressing others, to be upregulated in ACB compared to GCB DLBCL primary patient samples (p=5.1 x 10^-37). Knockdown of NFKBIZ by RNA interference was toxic to ABC but not GCB DLBCL cell lines. Gene expression profiling following NFKBIZ knockdown significantly downregulated a large number of NF-kB target genes, suggesting a central role in regulating NF-kB signaling. To further investigate the molecular mechanisms of how NFKBIZ mediates NF-kB signaling in ABC DLBCL, we performed immunoprecipitations and detected an interaction of NFKBIZ with both p50 and p52 NF-kB subunits, indicating that both the canonical and non-canonical NF-kB pathways are regulated by NFKBIZ. Collectively, our data imply that NFKBIZ is required for NF-kB signaling in ABC DLBCL and thus might represent a promising molecular target for future therapies. The complete dataset is comprised of three experiments with the male HBL-1 ABC DLBCL cell line: a) 8 paired GEP measurements after NFKBIZ inhibition by shRNA, b) 6 paired GEP measurements after applying the MLN inhibitor and c) 4 two-color measurements after applying a MALT inhibitor. This dataset includes 6 paired GEP measurements after applying the MLN inhibitor.

2013-07-22 | E-GEOD-46972 | biostudies-arrayexpress

Response of HK-2 cells to stimulation with IL6 and TNF-alpha (90 minutes)

Project description:Abstract: Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. We compared age-associated changes in global gene expression patterns in the human kidney with genome-wide maps of transcription factor occupancy in human cell lines to identify potential regulators of gene expression changes in the aging kidney. The strongest associations involved three inflammation-associated transcription factors: NFκB, STAT1 and STAT3. We found that the activity of these transcription factors increases with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFN-γ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We found that common DNA variants in the two genes that encode the subunits of the canonical NFκB transcription factor (RELA and NFKB1) showed significant associations with kidney function and chronic kidney disease in gene association studies, providing the first evidence for a direct link between genetic variation in NFκB and individual differences in age-related phenotypes in the kidney. Our results point to chronic inflammation, mediated by NFκB, STAT1 and STAT3, as a dominant mechanism influencing gene expression changes during kidney aging. Biological triplicate experiments were performed for each cytokine treatment condition or control treatment.

2015-07-01 | E-GEOD-68940 | biostudies-arrayexpress

Response of HK-2 cells to stimulation with IL6 and TNF-alpha (72 hours)

2015-07-01 | E-GEOD-68941 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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