The purpose of our study was to identify expression signatures and molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.
Sex, Specimen part
View SamplesSomatic 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.
ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4.
Specimen part
View SamplesThe goal of this study was to identify lncRNAs and novel transcripts that are differentially regulated in cutaneous squamous cell carcinoma (SCC) using RNA sequencing
Cancer-Associated Long Noncoding RNA SMRT-2 Controls Epidermal Differentiation.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
No sample metadata fields
View SamplesThe Scc2/Scc4 complex binds to broad nucleosome-free regions in the promoters of highly expressed genes. The cohesin loader is recruited to these sites by the RSC chromatin remodeling complex
The Scc2-Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions.
No sample metadata fields
View SamplesCohesin acetylation by Eco1 during DNA replication establishes sister chromatid cohesion. We show that acetylation makes cohesin resistant to Wapl activity from S-phase until mitosis. Wapl turns out to be a key regulator of cohesin dynamics on chromosomes by controling cohesin maintenance following its establishment in S-phase and its role in chromosome condensation.
Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.
No sample metadata fields
View SamplesThe transcriptional basis for disrupted epidermal differentiation arising from TP63 AEC mutations remains to be elucidated. Here we present an organotypic model of AEC dysfunction that phenocopies differentiation defects observed in AEC patient skin. Transcriptional analysis of model AEC tissue revealed impaired induction of differentiation regulators, including OVOL1, GRHL3, KLF4, PRDM1 and ZNF750. Genome wide binding analyses of TP63 during epidermal differentiation showed direct binding of OVOL1, GRHL3, and ZNF750 promoters suggesting AEC mutants prevent normal activation of these targets by direct transcriptional interference. Remarkably, exogenous ZNF750 restores impaired epidermal differentiation caused by AEC mutation. Thus, repression of ZNF750 is central to disrupted epidermal differentiation in model AEC tissue.
Genomic profiling of a human organotypic model of AEC syndrome reveals ZNF750 as an essential downstream target of mutant TP63.
Specimen part
View SamplesHistone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Previous studies have shown that a reduction on histone deacetylase (HDAC) activity results on the enhancement of some psychostimulant-induced behaviors. In the present study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant in addictive behavior. Our results support an specific role for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long lasting, drug-induced behavioral plasticity. To further investigate the molecular bases of sodium butyrate action on long-lasting behavioral responses to morphine, we screened for potential substrates of their interaction by performing a genome-wide comparison of the striatal transcriptome after chronic administration of morphine in the absence or presence of sodium butyrate.
Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Suppression of progenitor differentiation requires the long noncoding RNA ANCR.
Specimen part, Disease, Treatment
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