Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance

ABSTRACT: NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance

PROVIDER: PRJNA656115 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12417800_1.fastq.gz	Fastqsanger.gz
	SRR12417800_2.fastq.gz	Fastqsanger.gz
	SRR12417801_1.fastq.gz	Fastqsanger.gz
	SRR12417801_2.fastq.gz	Fastqsanger.gz
	SRR12417802_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance

Project description:Epigenetic alteration is a hallmark of aging, but it remains unclear if perturbation of transcription machineries may affect longevity. NELF-mediated pausing of RNA polymerase II (RNAPII) constitutes an important step in transcription regulation. We found that halving NELF-A level in heterozygous mutants or via neuronal-specific depletion of NELF-A improves locomotor activity, stress resistance and lifespan of Drosophila significantly. Mechanistically, lower NELF-A releases paused RNAPII to facilitate productive transcription of the heat-shock protein (Hsp) genes. Elevated HSPs attenuate the level of protein aggregation, reactive oxidative species, DNA damage and systemic inflammation in the brains of NELF-A depleted flies. This protection is conserved in human cells where NELF-A depletion confers improved resistance against oxidative stress. Reduced oxidative DNA damage allows the maintenance of H3K9me2-enriched heterochromatin, which represses the activation of specific retrotransposons during aging. Therefore, by regulating transcription of Hsp genes in the brains, NELF-A controls multiple aspects of aging in Drosophila.

2020-11-30 | GSE155940 | GEO

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [ChIP-seq]

Project description:NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [ChIP-seq]

| PRJNA656367 | ENA

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [RNA-seq]

Project description:NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [RNA-seq]

| PRJNA656368 | ENA

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [RNA-seq]

Project description:Comparison of differentially expressed genes in Day 50 adult heterozygous NELF-A*/+ mutant (BX) and control sibling (Sib) fly heads (2 replicates).

2020-11-30 | GSE155939 | GEO

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance [ChIP-seq]

Project description:Comparison of differential H3K9me2 enrichment in Day 50 adult heterozygous NELF-A*/+ mutant (BX) and control sibling (Sib) fly heads (2 biological replicates).

2020-11-30 | GSE155938 | GEO

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance.

Project description:NELF-mediated pausing of RNA polymerase II (RNAPII) constitutes a crucial step in transcription regulation. However, it remains unclear how control release of RNAPII pausing can affect the epigenome and regulate important aspects of animal physiology like aging. We found that NELF-A dosage regulates Drosophila healthspan: Halving NELF-A level in the heterozygous mutants or via neuronal-specific RNAi depletion improves their locomotor activity, stress resistance, and lifespan significantly. Conversely, NELF-A overexpression shortens fly lifespan drastically. Mechanistically, lowering NELF-A level facilitates the release of paused RNAPII for productive transcription of the heat-shock protein (Hsp) genes. The elevated HSPs expression in turn attenuates the accumulation of insoluble protein aggregates, reactive oxidative species, DNA damage and systemic inflammation in the brains of aging NELF-A depleted flies as compared to their control siblings. This pro-longevity effect is unique to NELF-A due to its higher expression level and more efficient pausing of RNAPII than other NELF subunits. Importantly, enhanced resistance to oxidative stress in NELF-A heterozygous mutants is highly conserved such that knocking down its level in human SH-SY5Y cells attenuates hydrogen peroxide-induced DNA damage and apoptosis. Depleting NELF-A reconfigures the epigenome through the maintenance of H3K9me2-enriched heterochromatin during aging, leading to the repression of specific retrotransposons like Gypsy-1 in the brains of NELF-A mutants. Taken together, we showed that the dosage of neuronal NELF-A affects multiple aspects of aging in Drosophila by regulating transcription of Hsp genes in the brains, suggesting that targeting transcription elongation might be a viable therapeutic strategy against age-onset diseases like neurodegeneration.

| S-EPMC8135010 | biostudies-literature

NELF regulates a promoter-proximal step distinct from RNA Pol II pause-release

Project description:RNA polymerase II (Pol II) is generally paused at promoter-proximal regions in most metazoans, and based on in vitro studies, this function has been attributed to the negative elongation factor (NELF). Here, we show that upon rapid depletion of NELF, Pol II fails to be released into gene bodies, stopping instead around the +1 nucleosomal dyad-associated region. The transition to the 2nd pause region is independent of positive transcription elongation factor P-TEFb. During the heat shock response, Pol II is rapidly released from pausing at heat shock induced genes, while most genes are paused and transcriptionally downregulated during the heat shock response. We find that both aspects of the heat shock response remain intact upon NELF loss. We find that NELF depletion results in global loss of cap-binding complex from chromatin without global reduction of nascent transcript 5’ cap stability. Thus, our studies implicate NELF functioning in early elongation complexes distinct from Pol II pause-release.

2020-03-09 | GSE144786 | GEO

Systemic lipolysis promotes healthspan in Drosophila melanogaster

Project description:Since healthspan-extending interventions such as caloric restriction or fasting robustly promote lipid catabolism, we investigated how lifespan and healthspan were affected by increased lipid catabolism via bmm (brummer, FBgn0036449), the major triglyceride hydrolase in Drosophila. Global overexpression of bmm strongly promoted lifespan extension as well as numerous markers of healthspan, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Increased Bmm robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER stress via improved proteostasis. Overexpression of bmm recapitulated major physiological changes associated with dietary restriction (DR) and conveyed its effects through dSir2. Taken together, these data show that bmm overexpression has broad beneficial effects on healthspan, and implicate lipolysis as a key node underlying the beneficial effects of dietary interventions known to improve healthspan.

2022-09-27 | GSE178816 | GEO

NELF-A phosphorylation site identification

Project description:NELF-A phosphorylation by P-TEFb is a key event in the pausing release. We conduct IMAC-LC-MS-MS to identified NELF-A phosphorylation site by activation P-TEFb kinase.

2016-03-23 | PXD003433 | Pride

NELF-dependent transcription activation

Project description:Jurkat T-cells were latently infected with a defective HIV provirus carrying a GFP reporer gene. The cells were superinfected with a lentiviral vector expressing shRNA to NELF-E. The impact of NELF-depletion on RNAP II distribution on cellular genes and the HIV provirus was measured by ChIP-Seq. Data sets contained between 45 and 56 million mapped reads Four samples were compared: Control shRNA, NELF-E shRNA, Control shRNA plus TNF-a, NELF-E shRNA plus TNF-a.

2014-03-26 | E-GEOD-47481 | biostudies-arrayexpress

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