This SuperSeries is composed of the SubSeries listed below.
Arabidopsis REF6 is a histone H3 lysine 27 demethylase.
Specimen part
View SamplesWe demonstrate that REF6/JMJ12 (RELATIVE OF EARLY FLOWERING 6/Jumonji domain-containing protein 12) is an H3K27me3 and H3K27me2 demethylase. Plants overexpressing REF6/JMJ12 resemble mutants defective in H3K27me3-mediated gene silencing. Genetic interaction tests indicate that REF6/JMJ12 acts downstream of H3K27me3 methyltransferases. Moreover, loss of REF6/JMJ12 leads to ectopic and increased H3K27me3 and decreased mRNA expression of a large spectrum of genes involved in development and hormone responses to stimuli.
Arabidopsis REF6 is a histone H3 lysine 27 demethylase.
Specimen part
View SamplesTen-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases.
Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.
Specimen part, Cell line
View SamplesTen-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases.
Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.
Specimen part
View SamplesPolycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2bs genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression.
Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.
Specimen part, Cell line
View SamplesWhole human fetal lung transcriptome profiles from estimated gestational ages 54 to 137 days post conception. Maternal cigarette smoking status is indicated by cotinine levels measured in the corresponding placenta.
Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.
Sex, Specimen part, Subject
View SamplesPeripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and preeclampsia from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Early pregnancy vitamin D status and risk of preeclampsia.
Sex, Race
View SamplesAutism Spectrum Disorder (ASD) is a common pediatric cognitive disorder with high heritability. Yet no single genetic variant has accounted for more than a small fraction of cases. We sought to determine whether we could classify patients as having ASD vs. controls solely based on a multi-gene expression profiling of their peripheral blood cells.
Characteristics and predictive value of blood transcriptome signature in males with autism spectrum disorders.
Sex, Disease, Race
View SamplesPeripheral whole blood transcriptome profiles of pregnant women enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
Sex, Specimen part, Treatment, Race
View Samples