This SuperSeries is composed of the SubSeries listed below.
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesWe analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator.
Sex, Subject
View SamplesThe eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1) or promoting the resolution of RAD-51 double stranded DNA filaments (rfs-1 and helq-1) suggest that jmjd-5 prevents the formation of stalled postsynaptic recombination intermediates and favors RAD-51 removal. As these phenotypes are all recapitulated by a catalytically inactive jmjd-5 mutant, we propose a novel role for H3K36me2 regulation during late steps of homologous recombination critical to preserve genome integrity. Overall design: RNA sequencing of N2 and jmjd-5(tm3735) at 20C and 25C at generation 1 (G1) and generation 6 (G6)
JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
Subject
View SamplesDisrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process.
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
Specimen part, Treatment
View SamplesBackground: The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate immune responses in vivo has not been established in humans. Methods: Twenty healthy adults were randomized to receive placebo or a single high dose of vitamin D3 (cholecalciferol) one hour after localized skin irradiation with an erythemogenic dose of ultraviolet radiation. Primary outcomes included skin redness, skin thickness, and tissue expression of inflammatory mediators (TNF- and iNOS). Secondary outcomes included microarray analyses. Results: As compared to placebo, subjects receiving vitamin D3 (200,000 IU) demonstrated reduced expression of TNF- (p=0.04) and iNOS (p=0.02) in skin biopsies 48 hours after ultraviolet light exposure. Demonstrated trends included reduced skin redness (p=0.17), and reduced skin thickness (p=0.09) in subjects receiving vitamin D3 (200,000 IU). Unsupervised clustering of individuals based on global gene expression revealed that subjects with enhanced skin barrier repair expression profiles had higher serum vitamin D3 levels (p=0.007), increased arginase expression (p=0.005), and a sustained reduction in skin redness (p=0.02) after treatment, as compared to subjects with enhanced inflammatory gene expression profiles.
Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.
Sex, Age, Specimen part, Race
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