This SuperSeries is composed of the SubSeries listed below.
Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.
Specimen part
View SamplesCell type-specific master transcription factors (MTFs) play vital roles in defining cell identity and function. However, the roles ubiquitous factors play in the specification of cell identity remain underappreciated. Here we show that all three subunits of the ubiquitous heterotrimeric CCAAT-binding NF-Y complex are required for the maintenance of embryonic stem cell (ESC) identity, and establish NF-Y as a novel component of the core pluripotency network. Genome-wide occupancy and transcriptomic analyses in ESCs and neurons reveal that not only does NF-Y regulate genes with housekeeping functions through cell type-invariant promoter-proximal binding, but also genes required for cell identity by binding to cell type-specific enhancers with MTFs. Mechanistically, NF-Y's distinctive DNA-binding mode promotes MTF binding at enhancers by facilitating a permissive chromatin conformation. Our studies unearth a novel function for NF-Y in promoting chromatin accessibility, and suggest that other proteins with analogous structural and DNA-binding properties may function in similar ways.
Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.
Specimen part
View SamplesGiven that the NF-B pathway plays an important role in tumor development and that IKK2 is the seminal kinase responsible for NF-B pathway activation, we were particularly interested in exploring the therapeutic potential of IKK2 inhibition in non-small cell lung cancers.
Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model.
Specimen part
View SamplesDespite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators.
Integrative framework for identification of key cell identity genes uncovers determinants of ES cell identity and homeostasis.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.
No sample metadata fields
View SamplesThe oocytes of most animals arrest at diplotene or diakinesis, but resume meiosis (meiotic maturation) in response to hormones. In C. elegans, maturation of the 1 oocyte requires the presence of sperm, Gas-adenylate cyclase-PKA signaling in the gonadal sheath cells, and germline function of two Tis11-like CCCH zinc-finger proteins, OMA-1 and OMA-2 (OMA proteins). Prior studies indicate that the OMA proteins redundantly repress the translation of specific mRNAs in oocytes (zif-1, mom-2, nos-2, glp-1) and early embryos (mei-1).
Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.
No sample metadata fields
View SamplesThe oocytes of most animals arrest at diplotene or diakinesis, but resume meiosis (meiotic maturation) in response to hormones. In C. elegans, maturation of the –1 oocyte requires the presence of sperm, Gas-adenylate cyclase-PKA signaling in the gonadal sheath cells, and germline function of two Tis11-like CCCH zinc-finger proteins, OMA-1 and OMA-2 (OMA proteins). Prior studies indicate that the OMA proteins redundantly repress the translation of specific mRNAs in oocytes (zif-1, mom-2, nos-2, glp-1) and early embryos (mei-1). We purified OMA-1-containing ribonucleoprotein particles (RNPs) and identified mRNAs that associate with OMA-1 in oocytes using microarrays. We examined the relative abundances of mRNAs in OMA-1 RNPs using high-throughput RNA sequencing. Previously identified targets of OMA-dependent translational repression in oocytes were found to be both enriched (>2-fold relative to input RNA) and abundant in purified OMA-1 RNPs. Furthermore, we verified that some of the newly identified mRNAs that share these characteristics are translationally repressed by OMA-1/2 in oocytes through sequences in their 3’UTRs. Although meiotic maturation is stimulated by sperm, we found that the mRNAs copurifying with OMA-1 are not significantly different in the presence and absence of sperm, suggesting that sperm-dependent signaling does not modify the suite of mRNAs stably associated with OMA-1. Further, several tested OMA-1-associated mRNAs were shown to be translationally repressed in both the presence and absence of sperm. Overall design: C. elegans mRNAs that co-purify with OMA-1 were identified by deep-sequencing using the Illumina HiSeq 2000
Translational control of the oogenic program by components of OMA ribonucleoprotein particles in Caenorhabditis elegans.
Subject
View SamplesWe analysed the capacity of THP-1 cells (differentiated to macrophagoid cells) to recognize RNA sequences via pattern recognition receptors in vitro. Gene expression was analysed by RNA-Microarray. Cytokine production was analysed by ELISA assays.
Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA.
Cell line, Treatment
View SamplesThe gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.
Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesWe used microarrays to investigate gene expression changes in leukemic cells from Pax5+/- mice treated with antibiotics.
An intact gut microbiome protects genetically predisposed mice against leukemia.
Sex, Specimen part, Treatment
View Samples