ERK3 is essential for establishment of epithelial architecture [ERK3 KD vs. TFAP2A KD]
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ABSTRACT:
PROVIDER: PRJNA433712 | ENA |
REPOSITORIES: ENA
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Project description:Establishment and maintenance of epithelial architecture are essential for embryonic development and adult physiology. Here, we show that ERK3, a poorly characterized atypical MAPK, regulates epithelial architecture in vertebrates. In Xenopus embryonic epidermal epithelia, ERK3 knockdown impairs adherens and tight junction protein distribution, as well as tight junction barrier function, resulting in epidermal breakdown. Moreover, in human breast epithelial cancer cells, inhibition of ERK3 expression induces thickened epithelia with aberrant adherens and tight junctions. Microarray results suggest an involvement of TFAP2A, a transcription factor important for epithelial gene expression, in ERK3-dependent gene expression changes. TFAP2A knockdown phenocopies ERK3 knockdown in both Xenopus embryos and human cells, and ERK3 is required for full activation of TFAP2A-dependent transcription. Our findings thus reveal that ERK3 regulates epithelial architecture, possibly in cooperation with TFAP2A. We used microarrays to compare the changes in ERK3-dependent gene expression profiles with those in TFAP2A-dependent gene expression profiles in Xenopus laevis embryos.
2018-06-13 | GSE110428 | GEO
Project description:Establishment and maintenance of epithelial architecture are essential for embryonic development and adult physiology. Here, we show that ERK3, a poorly characterized atypical MAPK, regulates epithelial architecture in vertebrates. In Xenopus embryonic epidermal epithelia, ERK3 knockdown impairs adherens and tight junction protein distribution, as well as tight junction barrier function, resulting in epidermal breakdown. Moreover, in human breast epithelial cancer cells, inhibition of ERK3 expression induces thickened epithelia with aberrant adherens and tight junctions. Microarray results suggest an involvement of TFAP2A, a transcription factor important for epithelial gene expression, in ERK3-dependent gene expression changes. TFAP2A knockdown phenocopies ERK3 knockdown in both Xenopus embryos and human cells, and ERK3 is required for full activation of TFAP2A-dependent transcription. Our findings thus reveal that ERK3 regulates epithelial architecture, possibly in cooperation with TFAP2A. We used microarrays to study the changes in ERK3-dependent gene expression profiles during pronephros and epidermal development in Xenopus laevis embryos.
2018-06-13 | GSE110427 | GEO
Project description:ERK3 is essential for establishment of epithelial architecture [ERK3 KD]
| PRJNA433711 | ENA
Project description:ERK3 is essential for establishment of epithelial architecture
| PRJNA433693 | ENA
Project description:The physiological functions and downstream effectors of the atypical mitogen-activated protein kinase ERK3 remain to be characterized. We recently reported that mice expressing catalytically-inactive ERK3 (Mapk6KD/KD) exhibit a reduced post-natal growth rate as compared to control mice. Here, we show that genetic inactivation of ERK3 impairs post-natal skeletal muscle growth and adult muscle regeneration after injury. Loss of MK5 phenocopies the muscle phenotypes of Mapk6KD/KD mice. At the cellular level, genetic or pharmacological inactivation of ERK3 or MK5 induces precocious differentiation of C2C12 or primary myoblasts, concomitant with MyoD activation. Reciprocally, ectopic expression of activated MK5 inhibits myogenic differentiation. Mechanistically, we show that MK5 directly phosphorylates FoxO3, promoting its degradation and reducing its association with MyoD. Depletion of FoxO3 rescues in part the premature differentiation of C2C12 myoblasts observed upon inactivation of ERK3 or MK5. Our findings reveal that ERK3 and its substrate MK5 act in a linear signaling pathway to control post-natal myogenic differentiation.
2021-12-04 | GSE190021 | GEO
Project description:RNA sequencing analysis of control and ERK3 knockdown HCPECs was performed to understand the physiological relevance of ERK3 in maintaining basal as well as LPS-mediated innate immune responses in HCPECs. Results revealed that ERK3 is required for the regulation of several key cytokines and chemokines even at the steady state. In particular, we discovered that ERK3 is indespansable for the transcriptional regulation of CXCL8/IL-8, CXCL10, MCP-1/CCL2 and GCP-2/CXCL6. Concomitantly, a functional interpretation of the differentially expressed (DE) genes with topGO indicated an important role of ERK3 in regulation of genes involved in, among others, immune responses and leukocyte chemotaxis.
2020-04-27 | GSE136002 | GEO
Project description:Mutations of the transcription factor TFAP2A are associated with congenital anomalies of the kidney and urinary tract in humans. In mice, deficiency of its ortholog Tfap2a in collecting duct cells causes widened epithelial tubules in the outer medulla of the adult kidney, but the molecular mechanisms of this phenotype are unknown. In this study, we identified gene regulatory networks controlled by Tfap2a in mouse kidney collecting ducts by combining gene knockout and transcriptomics. Integrated analyses of single-nucleus and bulk RNA-sequencing data from kidneys of adult Tfap2a knockout and control mice indicated deregulated expression of genes associated with cell adhesion and Wnt signaling pathways. Validation studies revealed that Tfap2a controls Wnt9b and Alcam, known regulators of kidney tubule morphogenesis. Our data provide novel insights into kidney epithelial gene regulatory networks controlled by Tfap2a and its potential functional role in congenital renal disease.
2025-08-08 | GSE290794 | GEO
Project description:Beta-adrenergic stimulation stabilizes ERK3, resulting in the formation of a complex with MK5 and thereby driving lipolysis. A downstream target of the complex is FOXO1, which controls expression of the lipolytic enzyme ATGL. Deletion of ERK3 in mouse adipocytes inhibits lipolysis, but elevates energy dissipation.
2021-01-01 | GSE142424 | GEO
Project description:Hypoxia can be established under pathological conditions, such as cancer, due to the imbalance between oxygen supply and consumption. Hypoxia Inducible Transcription Factor HIF-1 mediates the physiological response to hypoxia but also regulates multiple steps of carcinogenesis. Despite its well-defined oxygen-dependent activation, many aspects of HIF-1 transcriptional activity as well as interaction with chromatin remain elusive. We have recently shown that TFAP2A physically interacts with HIF-1 and hypoxia-dependent deSUMOylation of TFAP2A positively affects HIF-1 activity. We now present ChIP-seq analysis showing that TFAP2A resides together with HIF-1α on the promoters of a subset of hypoxia-regulated genes, the mRNA expression of which is downregulated by silencing of TFAP2A. Interestingly, CRISPR-mediated knockdown of TFAP2A expression under hypoxia decreased the occupancy of HIF-1α on these promoters and affected chromatin accessibility. Mechanistically, we reveal that the Ku70/Ku80 protein complex interacts with TFAP2A in a SUMO-dependent manner under hypoxia and participates in HIF-dependent gene expression. Moreover, using stable expression of TFAP2A forms that either lack or constitutively carry a SUMO modification, we could show that SUMOylation affects binding of TFAP2A to chromatin. Overall, our data suggest that TFAP2A is an important co-regulator of the HIF-1-dependent transcriptional response to hypoxia and SUMOylation fine-tunes this regulation. As both TFAP2A and HIF-1 play critical roles in cancer progression, a detailed characterization of their crosstalk could lead to novel therapeutic strategies for targeting and killing cancer cells in hypoxic tumors.
2025-05-23 | PXD053747 | Pride
Project description:Mutations of the transcription factor TFAP2A are associated with congenital anomalies of the kidney and urinary tract in humans. In mice, deficiency of its ortholog Tfap2a in collecting duct cells causes widened epithelial tubules in the outer medulla of the adult kidney, but the molecular mechanisms of this phenotype are unknown. In this study, we identified gene regulatory networks controlled by Tfap2a in mouse kidney collecting ducts by combining gene knockout and transcriptomics. Integrated analyses of single-nucleus and bulk RNA-sequencing data from kidneys of adult Tfap2a knockout and control mice indicated deregulated expression of genes associated with cell adhesion and Wnt signaling pathways. Validation studies revealed that Tfap2a controls Wnt9b and Alcam, known regulators of kidney tubule morphogenesis. Our data provide novel insights into kidney epithelial gene regulatory networks controlled by Tfap2a and its potential functional role in congenital renal disease.
2025-08-08 | GSE282959 | GEO