Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional contribution of nuclear lamina protein emerin and BAF in Drosophila ovaries

ABSTRACT: Nuclear lamina (NL) contributes to tissue homeostasis. In Drosophila, compromised NL blocks differentiation and causes loss of germline stem cells (GSCs) due to activation of the Chk2 checkpoint kinase. Checkpoint activation occurs upon loss of the NL protein Drosophila emerin or its partner Barrier-to-autointegration factor (BAF). As NL has long been thought to interact with specific genomic loci and regulate transcription, we examined transcriptional changes in emerin-/- and baf KD ovaries. We found thousands of genes are mis-regulated upon loss of emerin or BAF in GSCs. Remarkably, more than 90% of mis-regulated genes are shared between emerin-/- and baf KD. Finally, we show that transcriptional changes are downstream of Chk2 activation, as transcription are restored in chk2, emerin double mutant ovaries.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE168062 | GEO | 2021/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression analyses in otefin mutant Drosophila ovaries

Project description:LEM Domain proteins are key components of the nuclear lamina. Mutations in LEM-D proteins cause dystrophic diseases associated with compromised adult stem cells, yet it remains unclear how LEM-D proteins support stem cell function. Studies described here use the homologue of the LEM-D protein emerin in Drosophila, Otefin (Ote) as a model to understand LEM-D protein function in adult stem cells. Loss of Ote causes female sterility due to a complex germline stem cell (GSC) phenotype that includes both an early block in germline differentiation followed by GSC death. In vivo cell cycle analysis revealed that ote mutant GSCs display a lengthened S phase.We find that loss of the DNA Damage Response (DDR) Chk2 is able to not only rescue the lengthened S phase, but also GSC death and the block in germline differentiation. Activation of detrimental checkpoint in absence of Ote is conserved in both male and female GSCs and surprisingly occurs independent of detectable canonical DDR triggers, including transposon de-repression and DNA damage. Two defects were found to occur upstream of Chk2 activation: nuclear lamina morphological defects and altered heterochromatin organization. Together, our data identify the primary cause for a compromised adult stem cell population in the absence of a LEM-D protein.

2018-07-03 | GSE95309 | GEO

Transcriptional contribution of nuclear lamina protein emerin and BAF in Drosophila ovaries

Project description:Transcriptional contribution of nuclear lamina protein emerin and BAF in Drosophila ovaries

| PRJNA705972 | ENA

Transcription profiling of mouse Nbs1a??B/a??B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- animals reveals Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage

Project description:The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1âB/âB Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1âB/âB Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. Experiment Overall Design: Thymocytes from Wild type (Wt), Atm-/- and Chk2-/- mice were exposed to mock 5 Gy radiation (IR). The RNA was harvested 8 hours post treatment.

2008-06-20 | E-GEOD-11436 | biostudies-arrayexpress

Stochastic genome-nuclear lamina interactions: Modulating roles of Lamin A and BAF

Project description:The nuclear lamina (NL) is a filamentous layer lining the inner-nuclear-membrane (INM) that aids in the organization of the genome in large domains of low transcriptional activity. Recently, it was shown that the single-cell genome-NL interactions are much more dynamic than previously anticipated, which challenges the concept of the NL as a safe guard for transcriptional repressed genes. Here we discuss the role of the NL in light of these new findings and introduce Lamin A and BAF as potential modulators of LAD positioning BAF-chromatin and Lamin B2-chromatin interactions were assayed in human HT1080 by DamID on Nimblegen microarrays, with two biological replicates each, that were hybridized in a dye-swap design.

2014-02-15 | E-GEOD-55066 | biostudies-arrayexpress

Transcription profiling of Drosophila melanogaster germ line stem cells from bam mutant or Dpp overexpressing ovaries vs Kc cell controls

Project description:This series compares gene expression between germ line stem cells (GSCs) purified either from bam mutant or Dpp-overexpressing ovaries, with gene expression in Kc cells Experiment Overall Design: 3 replicates of GSCs from bam mutant ovaries Experiment Overall Design: 3 replicates of GSCs from Dpp overexpressing ovaries Experiment Overall Design: 3 replicates of Kc tissue culture cells

2007-10-31 | E-GEOD-2783 | biostudies-arrayexpress

Identification of PP2A-B55 targets in Drosophila uncovers regulation of Emerin during nuclear envelope reassembly

Project description:Entry into mitosis is triggered by mitotic kinases that phosphorylate multiple proteins to induce profound cellular changes including nuclear envelope breakdown, chromosome condensation and spindle assembly. Conversely, mitotic exit requires protein dephosphorylation as cells return to their interphase organization. Protein Phosphatase 2A in complex with its B55/Tws regulatory subunit (PP2A-B55) is known to play a crucial role in this transition. However, the precise events and substrates that it regulates are incompletely understood. We used proteomic approaches in Drosophila to identify proteins that interact with PP2A-B55 and are dephosphorylated in a PP2A-B55 dependent manner. Among several candidates, we identified Otefin (also known as Emerin) as a target of PP2A-B55 in the process of nuclear envelope reformation after mitosis. Emerin is a protein of the inner nuclear membrane that interacts with the DNA-binding protein Barrier-to-Autointegration Factor (BAF) via a LEM domain. Our results indicate that phosphorylation of Emerin at Ser50 and Ser54 near its LEM domain negatively regulates its association with BAF, Lamin and additional Emerin. Using live imaging, we show that dephosphorylation of Emerin at the identified sites determines the timing of nuclear envelope reformation. Genetic rescue experiments indicate that this regulation is required in vivo during embryonic development. Phosphoregulation of the Emerin-BAF complex formation by PP2A-B55 appears as a key event of mitotic exit that is likely to be conserved across species.

2023-08-10 | PXD041032 | Pride

Identification of PP2A-B55 targets in Drosophila uncovers regulation of Emerin during nuclear envelope reassembly

2023-08-10 | PXD041030 | Pride

Identification of PP2A-B55 targets in Drosophila uncovers regulation of Emerin during nuclear envelope reassembly

2023-08-10 | PXD041091 | Pride

Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage

Project description:The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. Keywords: Global gene expression analysis, response to radiation, Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mutant mice

2008-05-15 | GSE11436 | GEO

ZNF131 suppresses centrosome fragmentation in Glioblastoma stem-like cells through regulation of HAUS5

Project description:To identify new Glioblastoma multiforme (GBM) therapeutic strategies, we previously performed genome-wide RNAi lethality screens in patient-derived GBM stem-like cells (GSCs) and neural progenitor cells (NPCs) to identify genes required for the self-renewal of GSC isolates, but which are dispensable for NPCs. Here we report the retest of the GSC-lethal gene ZNF131, which encodes a novel vertebrate-specific BTB domain zinc finger transcription factor that is broadly required for GSC viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule (MT) nucleation along the mitotic spindle. Of these genes only kd of HAUS5 displayed GSC-specific viability loss, and, critically, HAUS5 ectopic expression was sufficient to suppress viability defects of ZNF131 kd cells. Moreover, ZNF131 and HAUS5 kd phenocopied each other in GSCs, each causing: mitotic arrest, centrosome fragmentation, loss of Augmin/HAUS complex on the mitotic spindle, and loss of GSC self-renewal and tumor formation capacity. In control NPCs, we observed centrosome fragmentation and lethality only when HAUS5 kd was combined with kd of HAUS2 or HAUS4, two other Augmin complex members, demonstrating that the complex is essential in NPCs, but that GSCs have heightened requirement. Our results suggest that GSCs differentially rely on ZNF131-dependent expression of HAUS5 as well as the Augmin/HAUS complex activity to maintain the integrity of centrosome function and viability. We speculate that this requirement likely arises from aneuploidy frequently observed in late stage GBM tumors, rather than supernumerary centrosomes.

2018-02-06 | GSE95027 | 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