TALE- and NF-Y-dependent Genes in 12 hpf Zebrafish Embryos
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE133459 | GEO | 2019/12/31
REPOSITORIES: GEO
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Project description:In contrast to stage-specific transcription factors, the role of ubiquitous transcription factors in neuronal development remains a matter of scrutiny. Here, we demonstrated that a ubiquitous factor NF-Y is essential for neural progenitor maintenance during brain morphogenesis. Deletion of the NF-YA subunit in neural progenitors by using nestin-cre transgene in mice resulted in significant abnormalities in brain morphology, including a thinner cerebral cortex and loss of striatum during embryogenesis. Detailed analyses revealed a progressive decline in multiple neural progenitors in the cerebral cortex and ganglionic eminences, accompanied by induced apoptotic cell death and reduced cell proliferation. In neural progenitors, the NF-YA short isoform lacking exon 3 is dominant and co-expressed with cell cycle genes. ChIP-seq analysis from the cortex during early corticogenesis revealed preferential binding of NF-Y to the cell cycle genes, some of which were confirmed to be downregulated following NF-YA deletion. Notably, the NF-YA short isoform disappears and is replaced by its long isoform during neuronal differentiation. Forced expression of the NF-YA long isoform in neural progenitors resulted in a significant decline in neuronal count, possibly due to the suppression of cell proliferation. Collectively, we elucidated a critical role of the NF-YA short isoform in maintaining neural progenitors, possibly by regulating cell proliferation and apoptosis. Moreover, we identified an isoform switch in NF-YA within the neuronal lineage in vivo, which may explain the stage-specific role of NF-Y during neuronal development.
2024-01-11 | GSE244758 | GEO
Project description:Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH2-terminal kinase (JNK) pathway exemplifies one sub-group of Mitogen-activated protein (MAP) kinases, which besides established functions in stress response, also contributes to developmental processes by an unknown mechanism 1-4. Here we show by genome-wide location analysis that JNK binds directly to a large set of active promoters during differentiation of stem cells to neurons. Bound promoters are not enriched for the canonical AP?1 target sites yet for binding motifs for the transcription factor NF?Y. NF-Y indeed occupies these predicted sites genome-wide in vivo and overexpression of a dominant-negative form of NF?YA reduces JNK presence on chromatin. Histone H3 is a substrate for JNK kinase activity in vitro and JNK bound promoters are preferentially enriched for Histone H3 phosphorylated at Serine 10. Inhibition of JNK signaling in postmitotic neurons reduces this chromatin phosphorylation as well as expression of target genes. Together this establishes MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation. Our Dataset comprises 5 ChIP-seq samples using chromatin from ES, NP and TN cells which was immunoprecipitated, using antibodies against H3K27me3, H3K4me2, RNA Pol II, JNK1/3 and NF-YA. From the same cells we generated biological replicates of RNA-seq data.
2011-12-18 | E-GEOD-25532 | biostudies-arrayexpress
Project description:The trimeric transcription factor -TF- NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. The NF-YC subunit was recently identified as an oncogene in choroid plexus carcinomas. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y comprehensively controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral, or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Within the different pathways, cancer-driving nodes are under NF-Y positive control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production, and other anabolic pathways commonly altered in cancer cells. Scrambled control (shSCM) and NF-YA pLKO.1-shRNAs were designed by Sigma-Aldrich. The puromycin resistance cassette was replaced with an EGFP cassette. Viral production and transduction were carried out as previously described (Benatti et al. 2011). H322 and HCT116 were transduced with shSC or shNF-YA viral supernatants, in triplicates and cells collected after 72 hours. RNA was prepared according to Affymetrix standard protocol and hybridized to Hu-Gene 2.0 expression arrays. H322 and HCT116 were transduced with shSC and shNF-YA and harvest after 72 hours
2016-07-03 | E-GEOD-70543 | biostudies-arrayexpress
Project description:NF-Y is a trimeric transcription factor whose binding site -the CCAAT box- is enriched in cancer-promoting genes. The regulatory subunit, the sequence-specificity conferring NF-YA, comes in two major isoforms, NF-YA long (NF-YAl) and short (NF-YAs). Extensive expression analysis in epithelial cancers determined two features: widespread overexpression and changes in NF-YAl/NF-Ys ratios (NF-YAr) in tumors with EMT features. We performed wet and in silico experiments to explore the role of the NF-YA isoforms in breast -BRCA- and gastric -STAD- cancers. We generated clones of two Claudinlow BRCA lines BT549 and SUM159PT ablated of exon-3, thus shifting expression from NF-YAl to NF-YAs. Edited clones show normal growth, but reduced migratory capacities in vitro, and ability to metastatize in vivo. Using TCGA, including upon deconvolution of scRNA-seq data, we formalize the clinical importance of high NF-YAr, associated to EMT genes and cell populations. We derive a novel, 158 genes signature common to BRCA and STAD Claudinlow tumors. Finally, we identify splicing factors associated to high NF-YAr, further validating RBFOX2 as promoting expression of NF-YAl with wet experiments. In conclusion, these data bring three relevant results: (i) concerning Claudinlow tumors, the definition and clinical implications of NF-YAr and the 158 genes signature; (ii) genetic evidence of a role of exon-3 28 aminoacids, empowering NF-YAl with EMT-driving features in BRCA. (iii) The definition of a set of splicing factors fine-tuning the levels of NF-YA isoforms.
2023-01-28 | GSE208088 | GEO
Project description:We knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and sorted brain striatal cells, and performed gene expression profiling. We found that the down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. These are highly contrast to the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed by NF-Y knockdown. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that transcriptomic difference was not correlated with the DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration rather than DNA-binding preference could be involved in this cell type-specific gene modulation.
2020-12-16 | GSE151146 | GEO
Project description:We knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and sorted brain striatal cells, and performed gene expression profiling. We found that the down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. These are highly contrast to the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed by NF-Y knockdown. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that transcriptomic difference was not correlated with the DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration rather than DNA-binding preference could be involved in this cell type-specific gene modulation.
2020-12-16 | GSE151145 | GEO
Project description:We knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and sorted brain striatal cells, and performed gene expression profiling. We found that the down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. These are highly contrast to the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed by NF-Y knockdown. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that transcriptomic difference was not correlated with the DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration rather than DNA-binding preference could be involved in this cell type-specific gene modulation.
2020-12-16 | GSE151275 | GEO
Project description:We knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and sorted brain striatal cells, and performed gene expression profiling. We found that the down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. These are highly contrast to the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed by NF-Y knockdown. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that transcriptomic difference was not correlated with the DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration rather than DNA-binding preference could be involved in this cell type-specific gene modulation.
2020-12-16 | GSE151144 | GEO
Project description:The transcription factor NF-Y promotes cell proliferation and often loses its activity during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant (NF-YAs) is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform (NF-YAl), majorly associated with cell differentiation. Through the generation of a conditional knock out mouse model that selectively ablates NF-YA in satellite cells, we demonstrate that NF-YA expression, and hence NF-Y activity, is fundamental to preserve the pool of muscle stem cells. Moreover, NF-Y supports their commitment to differentiation and ensures robust regenerative response to muscle injury. Gene expression profiling highlights an unexpected role for NF-Y in stem cell biology and opens a new scenario for NF-Y activity that is dispensable for muscle stem cell proliferation but required for efficient myogenic differentiation.
2021-08-30 | GSE154017 | GEO
Project description:Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH2-terminal kinase (JNK) pathway exemplifies one sub-group of Mitogen-activated protein (MAP) kinases, which besides established functions in stress response, also contributes to developmental processes by an unknown mechanism 1-4. Here we show by genome-wide location analysis that JNK binds directly to a large set of active promoters during differentiation of stem cells to neurons. Bound promoters are not enriched for the canonical AP?1 target sites yet for binding motifs for the transcription factor NF?Y. NF-Y indeed occupies these predicted sites genome-wide in vivo and overexpression of a dominant-negative form of NF?YA reduces JNK presence on chromatin. Histone H3 is a substrate for JNK kinase activity in vitro and JNK bound promoters are preferentially enriched for Histone H3 phosphorylated at Serine 10. Inhibition of JNK signaling in postmitotic neurons reduces this chromatin phosphorylation as well as expression of target genes. Together this establishes MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation.
2011-12-18 | GSE25532 | GEO