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Transcriptional repressor FOXD3 safeguards genome integrity in embryonic stem cells

ABSTRACT: Transcriptional repressor FOXD3 safeguards genome integrity in embryonic stem cells

PROVIDER: PRJNA760536 | ENA |

REPOSITORIES: ENA

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Genomic integrity safeguards pluripotency in embryonic stem cells

Project description:Genomic integrity safeguards pluripotency in embryonic stem cells

| PRJNA438830 | ENA

Transcriptional repressor FOXD3 safeguards genome integrity in embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-30 | GSE183420 | GEO

From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo

Project description:The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant versus wild-type cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3-expressing premigratory NC, our analysis shows that during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis-regulatory elements and reshuffling nucleosomes. Strikingly, foxd3 then gradually switches from an activator to its previously well-described role as a transcriptional repressor. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from ‘permissive’ to ‘repressive’ nucleosome/chromatin organisation to maintain multipotency and define cell fates.

2018-12-07 | GSE106676 | GEO

Characterization of FOXD3 cofactors by BioID

Project description:FOXD3 is essential in embryonic stem cells, however the primary molecular mechanism is unclear. Here, we performed BioID to identify proteins collaborating with FOXD3 in protecting embryonic stem cell survival.

2023-05-08 | PXD035284 | Pride

FOXD3 acts as a repressor of repeat elements in a heterochromatin-mediated pathway

Project description:Repeat element transcription plays a vital role in early embryonic development. Upregulation of repeats such as MERVL characterises the 2 cell-like population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify a the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription. FOXD3 binds to and recruits the histone methyl transferase Suv39h1 to MERVL and major satellite repeats in mouse embryonic stem cells, consequentially repressing the transcription of these repeats by establishment of the H3K9me3 heterochromatin modification. Notably, depletion of Foxd3 leads to the de-pression of MERVL and major satellite repeats and in turn the activation of a subset of genes expressed in the 2 cell state, shifting the balance between the stem cell and 2 cell-like population in culture. Thus FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.

2021-08-05 | GSE173602 | GEO

Foxd3 promotes the exit from naïve pluripotency and prevents germline specification through enhancer decommissioning [ChIP-Seq]

Project description:Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. Genome-wide binding profiles for Foxd3 were investigated in mouse embryonic stem cells (mESC). A mESC line (FH-Foxd3 mESC line) expressing exogenous Foxd3 tagged with Flag and HA epitope (FH-Foxd3) at nearly endogenous levels was generated. ChIPs were performed against FH-Foxd3 using anti-HA or anti-Flag antibodies.

2015-09-14 | E-GEOD-70545 | biostudies-arrayexpress

Genomic integrity safeguards pluripotency in embryonic stem cells

Project description:Illumina BeadChip array analyses of mouse embryonic stem cell gene expression profiles in the presence of or upon knockdown of 4 candidate factors regulating genomic integrity -- Chek1, Ppm1g, Ppp2r1b and Bub1b. An ES complementation 'rescue' system was employed to measure the effects of knockdown (minus Dox). The 4 candidate factors are rescued to wildtype levels in the presence of Dox (plus Dox). A control rescue ES cell line, with a Luciferase-targeting shRNA, was also assessed.

2018-11-01 | GSE111982 | GEO

JAK2-CHK2 signaling safeguards the integrity of the mitotic spindle assembly checkpoint and genome stability

Project description:This dataset consists of 1 raw MS file and associated peak list and result file, acquired on an Orbitrap Elite mass spectrometer operated in Data Dependent Acquisition mode. The files are associated with a manuscript submitted for publication. Publication title: "JAK2-CHK2 signaling safeguards the integrity of the mitotic spindle assembly checkpoint and genome stability"

2021-03-31 | MSV000087138 | MassIVE

FOXD3 suppresses tumor-initiating features in lung cancer via transcriptional repression of WDR5 and SET

Project description:In this study, we demonstrated that FOXD3, acting as a repressor in the expansion of lung cancer TICs, was negatively correlated with histological grades and metastasis in lung cancer, and provided evidence that FOXD3 repressed the TIC expansion, cell invasion and drug resistance in vivo and in vitro. Global genomic RNA-Seq and Chip-seq analyses identified WDR5 and SET as the direct targets of FOXD3 in lung cancer. Inhibition of WDR5 and SET could partially rescue TIC abundance, cell invasion, osteogenesis, and gene expression signature upon depletion of FOXD3. Clinically, we revealed that FOXD3 was negatively correlated with WDR5 and SET expression, CSC abundance, and prognosis of lung cancer.

2019-12-22 | GSE92735 | GEO

Foxd3 promotes the exit from naïve pluripotency and prevents germline specification through enhancer decommissioning [RNA-Seq]

2015-09-14 | GSE70546 | GEO