The epigenetic dynamics of induced pluripotent stem cell (iPSC) reprogramming in correctly reprogrammed cells at high resolution and throughout the entire process remain largely undefined. Here, we characterize conversion of mouse fibroblasts into iPSCs using Gatad2a-Mbd3/NuRD-depleted and highly efficient reprogramming systems. Unbiased high-resolution profiling of dynamic changes in levels of gene expression, chromatin engagement, DNA accessibility, and DNA methylation were obtained. We identified two distinct and synergistic transcriptional modules that dominate successful reprogramming, which are associated with cell identity and biosynthetic genes. The pluripotency module is governed by dynamic alterations in epigenetic modifications to promoters and binding by Oct4, Sox2, and Klf4, but not Myc. Early DNA demethylation at certain enhancers prospectively marks cells fated to reprogram. Myc activity drives expression of the essential biosynthetic module and is associated with optimized changes in tRNA codon usage. Our functional validations highlight interweaved epigenetic- and Myc-governed essential reconfigurations that rapidly commission and propel deterministic reprogramming toward naive pluripotency.
Pubmed ID: 30554962 RIS Download
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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsComputable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
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 mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
View all literature mentionsThis polyclonal targets MYC
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsThis polyclonal targets H3K36me3
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis polyclonal targets Mouse KLF4
View all literature mentionsThis polyclonal targets POLR2A
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis polyclonal targets POU5F1
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Mus musculus with name B6;129S-Tet2tm1.1Iaai/J from IMSR.
View all literature mentionsThis polyclonal targets Mouse KLF4
View all literature mentionsThis polyclonal targets MYC
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This polyclonal targets H3K9me3
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsMus musculus with name B6;129S-Tet2tm1.1Iaai/J from IMSR.
View all literature mentionsThis polyclonal targets POLR2A
View all literature mentionsThis polyclonal targets POU5F1
View all literature mentionsThis polyclonal targets H3K36me3
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentions