Search results for "TRANSCRIPTION FACTORS"
showing 10 items of 848 documents
Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations.
2016
Methyl-CpG binding protein 2 (MeCP2) is a widely abundant, multifunctional protein most highly expressed in post-mitotic neurons. Mutations causing Rett syndrome and related neurodevelopmental disorders have been identified along the entire MECP2 locus, but symptoms vary depending on mutation type and location. C-terminal mutations are prevalent, but little is known about the function of the MeCP2 C-terminus. We employ the genetic efficiency of Drosophila to provide evidence that expression of p.Arg294* (more commonly identified as R294X), a human MECP2 E2 mutant allele causing truncation of the C-terminal domains, promotes apoptosis of identified neurons in vivo. We confirm this novel find…
The broad phenotypic spectrum of PPP2R1A -related neurodevelopmental disorders correlates with the degree of biochemical dysfunction
2021
PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay …
Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice
2020
European journal of immunology 50(4), 515-524 (2020). doi:10.1002/eji.201948285
Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonicDrosophilabrain
2016
The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of theDrosophilabrain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner. Further, we reveal a novel role of DV genes—ventral …
Identification of accessory olfactory system and medial amygdala in the zebrafish
2017
AbstractZebrafish larvae imprint on visual and olfactory cues of their kin on day 5 and 6 postfertilization, respectively. Only imprinted (but not non-imprinted) larvae show strongly activated crypt (and some microvillous) cells demonstrated by pERK levels after subsequent exposure to kin odor. Here, we investigate the olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input. Imprinted larvae show a significantly increased activation of olfactory bulb cells compared to non-imprinted larvae after exposure to kin odor. Surprisingly, pERK activated Orthopedia-positive cell numbers in the intermediate ventral telencephalic nucl…
Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation
2017
MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR- 29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b…
Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis
2016
The Spalt-Like Transcription Factor 4 (SALL4) oncogene plays a central function in embryo-fetal development and is absent in differentiated tissues. Evidence suggests that it can be reactivated in several cancers worsening the prognosis. We aimed at investigating the risk associated with SALL4 reactivation for all-cause mortality and recurrence in cancer using the current literature. A PubMed and SCOPUS search until 1st September 2016 was performed, focusing on perspective studies reporting prognostic parameters in cancer data. In addition, 17 datasets of different cancer types from The Cancer Genome Atlas were considered. A total of 9,947 participants across 40 cohorts, followed-up for abo…
Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
2021
Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human t…
A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
2017
Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3(+) regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Here, we report that enhancing sympathetic tone by cold exposure, beta3-adrenergic receptor (ADRB3) stimulation or a short-term high-calorie diet enhances Treg induction in vitro and in vivo. CD4(+) T cell proteomes revealed higher expression of Foxp3 regulatory networks in response to cold or ADRB3 stimulation in vivo reflecting Treg induction. Specifically, Ragulator-interacting protein C17o…
Immunohistochemical analysis of NKX2.2, ETV4, and BCOR in a large series of genetically confirmed Ewing sarcoma family of tumors
2017
Ewing sarcoma is an aggressive neoplasm of pediatric and adolescent patients. Immunohistochemistry (IHC) can be used to support the morphologic diagnosis of Ewing sarcoma family of tumors (ESFT) in a convincing clinical/radiological context. Although neither NKX2.2 nor CD99 alone are entirely specific, when combined, the diagnostic specificity is high. The aim of the present study was to investigate the IHC expression of NKX2.2, ETV4 and BCOR in a large series of genetically confirmed ESFT. The results for CD99 and CAV-1 immunoreactivity, and the histological and fusion gene subtypes were retrieved from our previous study. NKX2.2 demonstrated moderate or strong nuclear positivity in 91.2% o…