Similar Datasets
Project description:Using RNA-seq technology, we aimed to provide insight into the consequences of the knockdown of Smarcb1, an essential esBAF subunit, for the gene expression of murine embryonic stem cells. We were able to show that knockdown cells show both, an upregulation and a downregulation, of a high number of genes. Further, many of these genes are connected to central cellular processes like cell organization or cell adhesion as well as to critical developmental processes like nervous system development.
2022-04-27 | GSE186668 | GEO
Project description:Using ChIP-seq technology, we aimed to provide insight into the consequences of the knockdown of Smarcb1, an essential esBAF subunit, for the binding of the esBAF complex (Smarca4), the PRC2 complex (Ezh2) as well as for histone marks H3K27me3, H3K27ac and H3K4me3. We show that Smarcb1 knockdown results in the change of BAF complex binding in both directions: decreased binding (potentially by loss of function) as well as increased binding (potentially by retargeting). Furthermore, we see that binding changes especially occur in regions important for basic cellular functions (adhesion, cell organization, metabolism) as well as regions crucial for development (especially nervous system development). In addition, we depicted binding changes in enhancer regions in which a decrease of BAF binding was much more prominent than in gene regions.
2022-04-27 | GSE186667 | GEO
Project description:The murine esBAF complex plays a major role in the regulation of gene expression during stem cell development and differentiation. As one of its core subunits, Smarcb1 is indispensable for its function and its loss is connected to neurodevelopmental disorders and participates in the carcinogenesis of entities such as rhabdoid tumours. We explored how Smarcb1 regulates gene programs in murine embryonic stem cells (mESC) and in this way orchestrates differentiation. Our data underline the importance of Smarcb1 expression and function for the development of the nervous system along with basic cellular functions, such as cell adhesion and cell organisation. Using ChIP-seq, we were able to portray the consequences of Smarcb1 knockdown (kd) for the binding of esBAF and PRC2 as well as its influence on histone marks H3K27me3, H3K4me3 and H3K27ac. Their signals are changed in gene and enhancer regions of genes connected to nervous system development and offers a plausible explanation for changes in gene expression. Further, we describe a group of genes that are, despite increased BAF binding, suppressed after Smarcb1 kd by mechanisms independent of PRC2 function.
| S-EPMC9027123 | biostudies-literature
Project description:Smarcb1 is indispensable for the nervous system development and its loss results in a deregulation of esBAF binding.
| PRJNA775001 | ENA
Project description:Smarcb1 is indispensable for the nervous system development and its loss results in a deregulation of esBAF binding [RNA-seq]
| PRJNA775007 | ENA
Project description:Smarcb1 is indispensable for the nervous system development and its loss results in a deregulation of esBAF binding [ChIP-seq]
| PRJNA775008 | ENA
Project description:Alzheimer's disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion of AD-associated A? oligomers (A?Os) in mice triggered peripheral glucose intolerance, a phenomenon further verified in two transgenic mouse models of AD. Systemically injected A?Os failed to induce glucose intolerance, suggesting A?Os target brain regions involved in peripheral metabolic control. Accordingly, we show that A?Os affected hypothalamic neurons in culture, inducing eukaryotic translation initiation factor 2? phosphorylation (eIF2?-P). A?Os further induced eIF2?-P and activated pro-inflammatory IKK?/NF-?B signaling in the hypothalamus of mice and macaques. A?Os failed to trigger peripheral glucose intolerance in tumor necrosis factor-? (TNF-?) receptor 1 knockout mice. Pharmacological inhibition of brain inflammation and endoplasmic reticulum stress prevented glucose intolerance in mice, indicating that A?Os act via a central route to affect peripheral glucose homeostasis. While the hypothalamus has been largely ignored in the AD field, our findings indicate that A?Os affect this brain region and reveal novel shared molecular mechanisms between hypothalamic dysfunction in metabolic disorders and AD.
| S-EPMC4328648 | biostudies-literature
Project description:Selenoproteins are a distinct class of proteins that are characterized by the co-translational incorporation of selenium (Se) in the form of the 21st amino acid selenocysteine. Selenoproteins provide a key defense against oxidative stress, as many of these proteins participate in oxidation-reduction reactions neutralizing reactive oxygen species, where selenocysteine residues act as catalytic sites. Many selenoproteins are highly expressed in the brain, and mouse knockout studies have determined that several are required for normal brain development. In parallel with these laboratory studies, recent reports of rare human cases with mutations in genes involved in selenoprotein biosynthesis have described individuals with an assortment of neurological problems that mirror those detailed in knockout mice. These deficits include impairments in cognition and motor function, seizures, hearing loss, and altered thyroid metabolism. Additionally, due to the fact that oxidative stress is a key feature of neurodegenerative disease, there is considerable interest in the therapeutic potential of selenium supplementation for human neurological disorders. Studies performed in cell culture and rodent models have demonstrated that selenium administration attenuates oxidative stress, prevents neurodegeneration, and counters cell signaling mechanisms known to be dysregulated in certain disease states. However, there is currently no definitive evidence in support of selenium supplementation to prevent and/or treat common neurological conditions in the general population. It appears likely that, in humans, supplementation with selenium may only benefit certain subpopulations, such as those that are either selenium-deficient or possess genetic variants that affect selenium metabolism.
| S-EPMC4222985 | biostudies-literature
Project description:SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors, and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome. Mouse models validated Smarcb1 as a bona fide tumor suppressor, as Smarcb1 inactivation in mice results in 100% of the animals rapidly developing cancer. SMARCB1 was the first subunit of the SWI/SNF complex found mutated in cancer. More recently, at least seven other genes encoding SWI/SNF subunits have been identified as recurrently mutated in cancer. Collectively, 20% of all human cancers contain a SWI/SNF mutation. Consequently, investigation of the mechanisms by which SMARCB1 mutation causes cancer has relevance not only for rhabdoid tumors, but also potentially for the wide variety of SWI/SNF mutant cancers. Here we discuss normal functions of SMARCB1 and the SWI/SNF complex as well as mechanistic and potentially therapeutic insights that have emerged.
| S-EPMC4195815 | biostudies-literature
Project description:The development of the central nervous system (CNS) is a complex orchestration of stem cells, transcription factors, growth/differentiation factors, and epigenetic control. Noncoding RNAs have been identified, classified, and studied for their functional roles in many systems including the CNS. In particular, the class of long noncoding RNAs (lncRNAs) has generated both enthusiasm and skepticism due to the unexpected discovery, the diversity of mechanisms, and the lower level of expression than found in protein-coding RNAs. Here we describe evidence supporting the role of lncRNAs in driving CNS-specific differentiation. It is clear that lncRNAs exhibit a functional diversity that makes their study and compartmentalization more challenging than other classes of noncoding RNAs. We predict, however, that lncRNAs will be essential for the characterization of discrete neuronal cell types in the age of single-cell transcriptomics and that these regulatory RNAs contribute to the multitude of functional mechanisms during CNS differentiation that will rival the diversities of protein-based mechanisms.
| S-EPMC5148644 | biostudies-literature