Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Requirement for flap endonuclease 1 (FEN1) to maintain genomic stability and transcriptional gene silencing in Arabidopsis

ABSTRACT: As a central component during Okazaki fragment maturation, flap endonuclease 1 (FEN1) removes the 5’ flap and maintains genomic stability. Here, FEN1 was cloned as a suppressor of transcriptional gene silencing (TGS) from a forward genetic screen. FEN1 is abundant in the root and shoot apical meristems and FEN1-GFP shows a nucleolus-localized signal in tobacco cells. Arabidopsis fen1-1 mutant is hypersensitive to MMS and shows reduced telomere length. Interestingly, genome-wide ChIP-seq and RNA-seq results demonstrate that FEN1 mutation leads to a decrease in the H3K27me3 level and an increase in the expression of a subset of genes marked with H3K27me3. Overall, these results uncover a role for FEN1 in mediating TGS besides maintaining genome stability in Arabidopsis.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE79738 | GEO | 2016/05/28

SECONDARY ACCESSION(S): PRJNA316877

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Requirement for flap endonuclease 1 (FEN1) to maintain genomic stability and transcriptional gene silencing in Arabidopsis

Project description:As a central component during Okazaki fragment maturation, flap endonuclease 1 (FEN1) removes the 5â flap and maintains genomic stability. Here, FEN1 was cloned as a suppressor of transcriptional gene silencing (TGS) from a forward genetic screen. FEN1 is abundant in the root and shoot apical meristems and FEN1-GFP shows a nucleolus-localized signal in tobacco cells. Arabidopsis fen1-1 mutant is hypersensitive to MMS and shows reduced telomere length. Interestingly, genome-wide ChIP-seq and RNA-seq results demonstrate that FEN1 mutation leads to a decrease in the H3K27me3 level and an increase in the expression of a subset of genes marked with H3K27me3. Overall, these results uncover a role for FEN1 in mediating TGS besides maintaining genome stability in Arabidopsis. To characterized the role of FEN1 in epigenetic silencing, we examine histone modification and RNA expression changes by whole-genome RNA sequencing; H3K27me3-, H3K4me3-, H3K9me2-, H3-ChIP-seq in A. thaliana transgenic wild type (TWT) and fen1 mutant

2016-05-28 | E-GEOD-79738 | biostudies-arrayexpress

RNA editing using the flap endonuclease 1 guided by hairpin DNA probes

Project description:Here we characterized a flap endonuclease 1 (FEN1) plus hairpin DNA probe (hpDNA) system, called the HpSGN system, for both DNA and RNA editing without sequence limitation.To investigate the mRNA on/off target cleavage effective of the HpSGN system,we co-transformed HepG2 (liver hepatocellular cells) with plasmids encoding FEN1 with NES and two groups of hpDNAs targeting the mRNA of AFP (Alpha Fetoprotein) gene and CDK9 (Cyclin-dependent kinase 9) gene, respectively. RNA-seq was used to examine the on/off taget cleavage effective.We proved the HpSGN system can knock down specific mRNAs in human cells at a level of ~25%.At the same time,it indicated that a degree of off-targets occur in HpSGN-treated cells.

2023-06-20 | GSE152883 | GEO

Gene regulation using the flap endonuclease 1 guided by mis-hairpin DNA probes

Project description:Here we characterized a genetic regulatory system named as the hpDNA-assisted structure-guided nuclease mediating interference (HpSGNi) system, which was composed of flap endonuclease 1 (FEN1) and mis-hairpin DNA probe (mis-hpDNA). To investigate gene regulation effective of the HpSGNi system, we co-transformed HEK293A (human embryonic kidney epithelial cells) with plasmids encoding FEN1 with NES and two groups of mis-hpDNAs targeting the EGFP gene and negative control, respectively. RNA-seq was used to examine the regulation effective. We proved the HpSGNi system can knock down specific gene in human cells. At the same time, it indicated that a degree of off-targets occur in HpSGNi-treated cells.

2024-04-11 | GSE171834 | GEO

Processing of eukaryotic Okazaki fragments by redundant nucleases can be uncoupled from ongoing DNA replication in vivo

Project description:Prior to ligation, each Okazaki fragment synthesized on the lagging strand in eukaryotes must be nucleolytically processed. Nuclease cleavage takes place in the context of 5’ flap structures generated via strand-displacement synthesis by DNA polymerase delta. At least three DNA nucleases: Rad27 (Fen1), Dna2, and Exo1, have been implicated in processing Okazaki fragment flaps. However, neither the contributions of individual nucleases to lagging-strand synthesis nor the structure of the DNA intermediates formed in their absence have been clearly defined in vivo. By conditionally depleting lagging-strand nucleases and directly analyzing Okazaki fragments synthesized in vivo in S. cerevisiae, we conduct a systematic evaluation of the impact of Rad27, Dna2 and Exo1 on lagging-strand synthesis. We find that Rad27 processes the majority of lagging-strand flaps, with a significant additional contribution from Exo1 but not from Dna2. When nuclease cleavage is impaired, we observe a reduction in strand-displacement synthesis as opposed to the widespread generation of long Okazaki fragment 5’ flaps, as predicted by some models. Further, using cyclin-controlled constructs, we demonstrate that both the nucleolytic processing and the ligation of Okazaki fragments can be uncoupled from DNA replication and delayed until after synthesis of the majority of the genome is complete.

2018-08-04 | GSE118078 | GEO

Arabidopsis thaliana

Project description:Requirement for flap endonuclease 1 (FEN1) to maintain genomic stability and transcriptional gene silencing in Arabidopsis

| PRJNA316877 | ENA

DNA structure-specific endonuclease FEN1 as a novel drug target in tamoxifen resistant breast cancer.

Project description:Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patient prognostication. FEN1 levels were predictive of outcome in tamoxifen-treated patients, and FEN1 played a causal role in ERα-driven cell growth. FEN1 impacted the transcriptional-activity of ERα by facilitating coactivator recruitment to the ERα transcriptional complex. FEN1 blockade induced proteasome-mediated degradation of activated ERα, resulting in loss of ERα-driven gene expression and eradicated tumor cell proliferation. Finally, a high-throughput 465,195 compound screen identified a novel FEN1 inhibitor, which effectively blocked ERα-function and inhibited proliferation of tamoxifen-resistant cell lines as well as ex-vivo cultured ERα-positive breast tumors. Collectively, these results provide therapeutic proof-of-principle for FEN1 blockade in tamoxifen-resistant breast cancer.

2020-06-01 | GSE95302 | GEO

Identification of flap structure specific endonuclease 1 as a factor involved in LTM formation of aversive learning

Project description:We proposed that DNA recombination/repair processes play a role in memory formation. Here, we used microarray analysis of rat amygdala genes to identify possible DNA recombination/repair factors involved in memory consolidation of conditioned taste aversion (CTA). Among the genes that showed statistically significant differential expression, we identified fen-1, encoding a flap-structure specific DNA endonuclease. Amygdalar fen-1 mRNA induction was associated to the illness component of CTA, since it could be observed by the pairing of a flavor and gastrointestinal illness, by the illness itself, but not by the presentation of the flavor alone. No CTA related induction of fen-1 expression was observed in the insular cortex. Importantly, functional validation studies demonstrated that amygdalar suppression of fen-1 expression impaired memory consolidation of CTA. Overall, our studies helped identify a new DNA recombination/repair candidate factor involved in memory formation of aversive experiences.

2009-12-30 | GSE11520 | GEO

Identification of flap structure specific endonuclease 1 as a factor involved in LTM formation of aversive learning

2009-12-30 | E-GEOD-11520 | biostudies-arrayexpress

The RPB2 flap loop of human RNA polymerase II is dispensable for transcription initiation and elongation.

Project description:Deletion of the flap loop in the Rp2 subunit of human RNAPII did not alter the ability of human RNAPII to initiate transcription or elongate the initiated transcripts in vivo and in vitro, and was also dispensable for elongation factor-mediated enhancement and inhibition of transcript elongation in vitro. ChIP:chip of wild-type and flap deletion human RNAPII revealed that the mutant RNAPII was not defective for promoter binding, initiation and elongation in vivo.

2011-06-24 | GSE29734 | GEO

A stress-induced error prone 3’ flap-based Okazaki fragment maturation pathway creates internal tandem duplications for cell survival (WGS)

Project description:Faithful and efficient Okazaki fragment maturation is the key to maintain the genome integrity. In addition, this process is coupled with deposition of histone proteins. Therefore, functional deficiency in Okazaki fragment maturation may cause genome instablities as well and epigenetic alterations. We conduct WGS of WT and rad27 knockout yeast strains to define the DNA mutations caused by defective Okazaki fragment muturaton and conduct RNA-seq to define the changes in gene expression profiling due to defetive Okazaki fragment muturations..

2021-11-01 | GSE178875 | GEO

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