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Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance.

Cell stem cell | 2019

The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders.

Pubmed ID: 30849367 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: UM1 HG009409
  • Agency: Medical Research Council, United Kingdom
    Id: FC0010089
  • Agency: NCI NIH HHS, United States
    Id: P30 CA034196
  • Agency: NIDDK NIH HHS, United States
    Id: U54 DK107967
  • Agency: Wellcome Trust, United Kingdom
    Id: FC0010089
  • Agency: Cancer Research UK, United Kingdom
    Id: FC0010089
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/K005316/1
  • Agency: Wellcome Trust, United Kingdom

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This is a list of tools and resources that we have found mentioned in this publication.


Zebrafish Information Network (ZFIN) (tool)

RRID:SCR_002560

Model organism database that serves as central repository and web-based resource for zebrafish genetic, genomic, phenotypic and developmental data. Data represented are derived from three primary sources: curation of zebrafish publications, individual research laboratories and collaborations with bioinformatics organizations. Data formats include text, images and graphical representations.Serves as primary community database resource for laboratory use of zebrafish. Developed and supports integrated zebrafish genetic, genomic, developmental and physiological information and link this information extensively to corresponding data in other model organism and human databases.

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Covance (tool)

RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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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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GeneTools (tool)

RRID:SCR_005663

Web-service providing access to database that brings together information from broad range of resources. Web application for functional annotation and statistical hypothesis testing. Provides tools for analysis of genomic and microarray data. Collection of tools include Bibliographic Information,Databases,Gene Annotation,Gene Regulation, Microarray,Proteins,Sequence Manipulation - Nucleic Acids,Sequence Manipulation - Protein, Systems Biology.

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BD CellQuest Pro (tool)

RRID:SCR_014489

A software for acquiring and analyzing flow cytometry data. The user can create plots with elements like regions, gates, statistics, markers, and annotated text. The software can also be used for batch analysis or quality control of analysis. Results can be exported and saved.

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Sox-2 (Y-17) Antibody (antibody)

RRID:AB_2286684

This polyclonal targets SOX2

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MACS (software resource)

RRID:SCR_013291

Software 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.

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STOCK Sox2tm4.1Skn/Cnrm (organism)

RRID:IMSR_EM:07995

Mus musculus with name STOCK Sox2tm4.1Skn/Cnrm from IMSR.

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RRID:SCR_005476

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RSEM (software resource)

RRID:SCR_013027

Software package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.

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NOISeq (software resource)

RRID:SCR_003002

Software used for the identification of differentially expressed genes from count data or previously normalized count data. It empirically models the noise distribution of count changes by contrasting fold-change differences (M) and absolute expression differences (D) for all the features in samples within the same condition. This reference distribution is then used to assess whether the M-D values computed between two conditions for a given gene is likely to be part of the noise or represent a true differential expression.

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NOISeq (software resource)

RRID:SCR_003002

Software used for the identification of differentially expressed genes from count data or previously normalized count data. It empirically models the noise distribution of count changes by contrasting fold-change differences (M) and absolute expression differences (D) for all the features in samples within the same condition. This reference distribution is then used to assess whether the M-D values computed between two conditions for a given gene is likely to be part of the noise or represent a true differential expression.

View all literature mentions

RSEM (software resource)

RRID:SCR_013027

Software package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.

View all literature mentions

Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

View all literature mentions

MACS (software resource)

RRID:SCR_013291

Software 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 mentions

MACS (software resource)

RRID:SCR_013291

Software 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 mentions

Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

View all literature mentions