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Here, we report DNA methylation and hydroxymethylation dynamics at nucleotide resolution using C/EBPα-enhanced reprogramming of B cells into induced pluripotent cells (iPSCs). We observed successive waves of hydroxymethylation at enhancers, concomitant with a decrease in DNA methylation, suggesting active demethylation. Consistent with this finding, ablation of the DNA demethylase Tet2 almost completely abolishes reprogramming. C/EBPα, Klf4, and Tfcp2l1 each interact with Tet2 and recruit the enzyme to specific DNA sites. During reprogramming, some of these sites maintain high levels of 5hmC, and enhancers and promoters of key pluripotency factors become demethylated as early as 1 day after Yamanaka factor induction. Surprisingly, methylation changes precede chromatin opening in distinct chromatin regions, including Klf4 bound sites, revealing a pioneer factor activity associated with alternation in DNA methylation. Rapid changes in hydroxymethylation similar to those in B cells were also observed during compound-accelerated reprogramming of fibroblasts into iPSCs, highlighting the generality of our observations.
Pubmed ID: 30220521 RIS Download
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Java toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsThis monoclonal targets CD16 / CD32
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets Rabbit
View all literature mentionsThis polyclonal targets
View all literature mentionsThis monoclonal targets Human ERR beta / NR3B2
View all literature mentionsThis polyclonal targets Human TFCP2L1
View all literature mentionsThis monoclonal targets beta-Tubulin I antibody produced in mouse
View all literature mentionsThis polyclonal targets Mouse KLF4
View all literature mentionsThis monoclonal targets C/EBP alpha (14AA)
View all literature mentionsThis polyclonal targets Tet2
View all literature mentionsThis monoclonal targets 5-methylcytosine
View all literature mentionsThis polyclonal targets 5-Hydroxymethylcytosine (5-hmC)
View all literature mentionsThis polyclonal targets H3K4me2
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Tet2tm1.1Iaai/J from IMSR.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsSoftware package for noise-robust soft clustering of gene expression time-series data (including a graphical user interface).
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Retrieve-ensembl-seq is included in the software suite regulatory sequence analysis tools (RSAT), allowing instant submission of retrieved sequences to further analysis tools. AVAILABILITY: retrieve-ensembl-seq is integrated in the RSAT suite: http://rsat.ulb.ac.be/rsat. Web site: http://rsat.ulb.ac.be/rsat/retrieve-ensembl-seq_form.cgi. Web services: http://rsat.ulb.ac.be/rsat/web_services/RSATWS.wsdl. Stand-alone distribution: freely available under an academic licence to download from the RSAT web site. The complete manual, a convenient tutorial and demos are available from the RSAT website. Additional help can be found on the RSAT public forum.
View all literature mentionsA suite of tools to address common questions raised in genomic studies - mostly with regard to overlap and proximity relationships between data sets.
View all literature mentionsSoftware Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.
View all literature mentionsPython based tools to process, visualize and analyse high-throughput sequencing data, such as ChIP-seq, RNA-seq or MNase-seq. Implemented within Galaxy framework. Used to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsCell line S17 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line Plat-E is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ES-E14TG2a is a Embryonic stem cell with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name B6.Cg-Tg(Mx1-cre)1Cgn/J from IMSR.
View all literature mentionsMus musculus with name B6;129S-Tet2tm1.1Iaai/J from IMSR.
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