Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA153127 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Somatic progenitors suppress differentiation to maintain tissue self-renewal. While epigenetic regulators of DNA and histone modifications can support such repression, a role for nuclear actin-like proteins is unclear. In epidermis, ACTL6a/BAF53A was found enriched in progenitors and down-regulated during differentiation. Conditional ACTL6a deletion abolished epidermal self-renewal and induced terminal differentiation, whereas ectopically expressed ACTL6a suppressed differentiation. Among known activators of epidermal differentiation, KLF4 was found to control 227 genes also regulated by ACTL6a. ACTL6a loss upregulated KLF4 and its target genes, effects that were blocked by KLF4 depletion. Among multiple ACTL6a-interacting epigenetic regulators, the SWI/SNF complex was required for KLF4 activation and differentiation. In progenitors, ACTL6a loss led to enhanced SWI/SNF binding to the promoters of KLF4 and other differentiation genes. ACTL6a thus maintains the undifferentiated progenitor state, in part by suppressing SWI/SNF complex-enabled induction of KLF4. Gene expression analysis: To identify the gene set controlled by ACTL6a in human keratinocyte. Total RNA was isolated in biologic duplicate from cells with ACTL6a loss as compared to controls, and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-11-30 | E-GEOD-36222 | biostudies-arrayexpress
Project description:Somatic progenitors suppress differentiation to maintain tissue self-renewal. While epigenetic regulators of DNA and histone modifications can support such repression, a role for nuclear actin-like proteins is unclear. In epidermis, ACTL6a/BAF53A was found enriched in progenitors and down-regulated during differentiation. Conditional ACTL6a deletion abolished epidermal self-renewal and induced terminal differentiation, whereas ectopically expressed ACTL6a suppressed differentiation. Among known activators of epidermal differentiation, KLF4 was found to control 227 genes also regulated by ACTL6a. ACTL6a loss upregulated KLF4 and its target genes, effects that were blocked by KLF4 depletion. Among multiple ACTL6a-interacting epigenetic regulators, the SWI/SNF complex was required for KLF4 activation and differentiation. In progenitors, ACTL6a loss led to enhanced SWI/SNF binding to the promoters of KLF4 and other differentiation genes. ACTL6a thus maintains the undifferentiated progenitor state, in part by suppressing SWI/SNF complex-enabled induction of KLF4.
2012-11-30 | GSE36222 | GEO
Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.
2016-11-18 | GSE88859 | GEO
Project description:ACTL6a is an essential component of SWI/SNF and expressed on the chromosome 3q26 cytoband, which is amplified in head and neck squamous cell carcinomas (HNSCC). While ACTL6A is emerging as an oncogene, its role as a treatment target and mechanisms of transcription factor induction remain unknown. Here, we show that ACTL6A expression is a mediator of the Warburg effect, with ACTL6A knockdown inducing mitochondrial dependency and significantly decreasing levels of aerobic glycolysis. Using ATAC-seq, we identify ACTL6A as a mediator of chromatin accessibility of AP-1 transcription factor sites and find that it regulates upstream MAPK signaling through induction Ras and Galectin-1. These effects sensitize ACTL6A over-expressing cells to inhibition of glycolysis by MEK inhibitors. Our results link SWI/SNF subunit amplification with potentiation of MAPK signaling in HNSCC and provide a novel mechanism by which cancer cells drive aerobic glycolysis and reduce mitochondrial dependency.
2025-08-25 | GSE305164 | GEO
Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of HNSCC cells with and without ablated endogenous ACTL6A via lentiviral shRNA.
2016-11-18 | GSE88831 | GEO
Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of untransformed keratinocytes (HaCaT) with and without ablated endogenous p63 via lentiviral shRNA.
2016-11-18 | GSE88832 | GEO
Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of HNSCC cells with and without ablated endogenous p63 via lentiviral shRNA
2016-11-18 | GSE88833 | GEO
Project description:Cilia are important subcellular organelles and are regulated by transcription factors including Foxj1 and Rfx proteins. Whether and how are cilia regulated at epigenetic level remains unknown. We addressed this question by knocking down or knocking out of chromatin remodeling genes. Interestingly, depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) complexes lead to ciliopathy-like phenotypes in zebrafish embryos. Specifically, depletion of Actl6a, one of the components of the SWI/SNF complexes lead cilia disassembly and cystic kidney, but do not affect cilia motility. Omics studies show that in Actl6a-depleted embryos, a set of cilia genes including Foxj1a and Rfx2, the master regulators of cilia assembly, were downregulated at transcriptional level, chromatin accessibility and the SWI/SNF complexes binding. Thus, our study reveals that the SWI/SNF complexes regulate cilia stability and kidney development by direct modulating the expression Foxj1a and Rfx2.
2026-01-01 | GSE277564 | GEO
Project description:Cilia are important subcellular organelles and are regulated by transcription factors including Foxj1 and Rfx proteins. Whether and how are cilia regulated at epigenetic level remains unknown. We addressed this question by knocking down or knocking out of chromatin remodeling genes. Interestingly, depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) complexes lead to ciliopathy-like phenotypes in zebrafish embryos. Specifically, depletion of Actl6a, one of the components of the SWI/SNF complexes lead cilia disassembly and cystic kidney, but do not affect cilia motility. Omics studies show that in Actl6a-depleted embryos, a set of cilia genes including Foxj1a and Rfx2, the master regulators of cilia assembly, were downregulated at transcriptional level, chromatin accessibility and the SWI/SNF complexes binding. Thus, our study reveals that the SWI/SNF complexes regulate cilia stability and kidney development by direct modulating the expression Foxj1a and Rfx2.
2026-01-01 | GSE277562 | GEO
Project description:Cilia are important subcellular organelles and are regulated by transcription factors including Foxj1 and Rfx proteins. Whether and how are cilia regulated at epigenetic level remains unknown. We addressed this question by knocking down or knocking out of chromatin remodeling genes. Interestingly, depletion of multiple components of the switch/sucrose non-fermentable (SWI/SNF) complexes lead to ciliopathy-like phenotypes in zebrafish embryos. Specifically, depletion of Actl6a, one of the components of the SWI/SNF complexes lead cilia disassembly and cystic kidney, but do not affect cilia motility. Omics studies show that in Actl6a-depleted embryos, a set of cilia genes including Foxj1a and Rfx2, the master regulators of cilia assembly, were downregulated at transcriptional level, chromatin accessibility and the SWI/SNF complexes binding. Thus, our study reveals that the SWI/SNF complexes regulate cilia stability and kidney development by direct modulating the expression Foxj1a and Rfx2.
2026-01-01 | GSE274953 | GEO