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The transcriptional and epigenomic foundations of ground state pluripotency.

Hendrik Marks | Tüzer Kalkan | Roberta Menafra | Sergey Denissov | Kenneth Jones | Helmut Hofemeister | Jennifer Nichols | Andrea Kranz | A Francis Stewart | Austin Smith | Hendrik G Stunnenberg
Cell | 2012

Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" postulated to establish a naive ground state. We show that the transcriptome and epigenome profiles of serum- and 2i-grown ES cells are distinct. 2i-treated cells exhibit lower expression of lineage-affiliated genes, reduced prevalence at promoters of the repressive histone modification H3K27me3, and fewer bivalent domains, which are thought to mark genes poised for either up- or downregulation. Nonetheless, serum- and 2i-grown ES cells have similar differentiation potential. Precocious transcription of developmental genes in 2i is restrained by RNA polymerase II promoter-proximal pausing. These findings suggest that transcriptional potentiation and a permissive chromatin context characterize the ground state and that exit from it may not require a metastable intermediate or multilineage priming.

Pubmed ID: 22541430

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MC_PC_12009
  • Agency: Wellcome Trust, United Kingdom
    Id: 079249
  • Agency: Medical Research Council, United Kingdom
    Id: G1100526
  • Agency: Medical Research Council, United Kingdom
    Id: G1001028
  • Agency: Medical Research Council, United Kingdom
    Id: G0800784

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Genomatix Software: Understanding Gene Regulation (tool)

RRID:SCR_008036

Genomatix is a privately held company that offers software, databases, and services aimed at understanding gene regulation at the molecular level representing a central part of systems biology. Its multilayer integrative approach is a working implementation of systems biology principles. Genomatix combines sequence analysis, functional promoter analysis, proprietary genome annotation, promoter sequence databases, comparative genomics, scientific literature data mining, pathway databases, biological network databases, pathway analysis, network analysis, and expression profiling into working solutions and pipelines. It also enables better understanding of biological mechanisms under different conditions and stimuli in the biological context of your data. Some of Genomatix'' most valuable assets are the strong scientific background and the years of experience in research & discovery as well as in development & application of scientific software. Their firsthand knowledge of all the complexities involved in the in-silico analysis of biological data makes them a first-rate partner for all scientific projects involving the evaluation of gene regulatory mechanisms. The Genomatix team has more than a decade of scientific expertise in the successful application of computer aided analysis of gene regulatory networks, which is reflected by more than 150 peer reviewed scientific publications from Genomatix'' scientists More than 35,000 researchers in industry and academia around the world use this technology. The software available in Genomatix are: - GenomatixSuite: GenomatixSuite is our comprehensive software bundle including ElDorado, Gene2Promoter, GEMS Launcher, MatInspector and MatBase. GenomatixSuite PE also includes BiblioSphere Pathway Edition. Chromatin IP Software - RegionMiner: Fast, extensive analysis of genomic regions. - ChipInspector: Discover the real power of your microarray data. Genome Annotation Software - ElDorado: Extended Genome Annotation. - Gene2Promoter: Retrieve & analyze promoters - GPD: The Genomatix Promoter Database, which is now included with Gene2Promoter. Knowledge Mining Software - BiblioSpere : The next level of pathway/genomics analysis. - LitInspector: Literature and pathway analysis for free. Sequence Analysis Software - GEMS Launcher: Our integrated collection of sequence analysis tools. - MalInspector: Search transcription factor binding sites - MatBase: The transcription factor knowledge base. Other (no registration required) Software - DiAlign: Multiple alignment of DNA/protein sequence. - Genomatix tools: Various small tools for sequence statistics, extraction, formatting, etc.

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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RefSeq (tool)

RRID:SCR_003496

Collection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.

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Arcturus Cellect Laser Capture Microdissection System (tool)

RRID:SCR_018641

Laser capture microdissection system that includes infrared lasers. It can be used for laser capture microdissection LCM, ultraviolet UV laser cutting, sanger sequencing, next generation sequencing, and quantitative PCR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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