Unknown,Transcriptomics,Genomics,Proteomics

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A draft map of cis-regulatory sequences in the mouse genome [ChIP-Seq]

ABSTRACT: As the most widely used mammalian model organism, mice play a critical role in biomedical research for mechanistic study of human development and diseases. Today, functional sequences in the mouse genome are still poorly annotated a decade after its initial sequencing. We report here a map of nearly 300,000 cis-regulatory sequences in the mouse genome, representing active promoters, enhancers and CTCF binding sites in a diverse set of 19 tissues and cell types. This map provides functional annotation to nearly 11% of the genome, and over 70% of conserved, non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we demonstrate that cis-regulatory sequences are organized into domains of coordinately regulated enhancers and promoters. Our results provide a valuable resource for the annotation of functional elements in the mammalian genome, and study of regulatory mechanisms for tissue-specific gene expression. 19 tissues and primary cell types were examined.

ORGANISM(S): Mus musculus

SUBMITTER: Bing Ren

PROVIDER: E-GEOD-29218 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A map of the cis-regulatory sequences in the mouse genome.

Shen Yin Y Yue Feng F McCleary David F DF Ye Zhen Z Edsall Lee L Kuan Samantha S Wagner Ulrich U Dixon Jesse J Lee Leonard L Lobanenkov Victor V VV Ren Bing B

Nature 20120801 7409

The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 10(9) bases of the mouse genome possess a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics ...[more]

PMID: 22763441

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Project description:Understanding the regulatory genome remains a significant challenge. Annotation of regulatory elements and identification of the transcription factors (TFs) targeting these elements are key steps in understanding how a given cell interprets its genetic blueprint. One goal of the modENCODE (model organism Encyclopedia of DNA Elements) project is to survey a diverse sampling of TFs, both DNA-binding and non-DNA binding factors, to provide a framework for the subsequent study of the mechanisms by which transcriptional regulators target the genome. Here we provide an updated map of the Drosophila melanogaster regulatory genome based on the location of 84 TFs at various stages of development. This regulatory map reveals a variety of genomic targeting patterns, including factors with strong preferences toward proximal promoter binding, factors that target intergenic and intronic DNA, and factors with distinct chromatin state preferences. The data also suggest the existence of a partially self-contained Polycomb regulatory network, and highlight the importance of Trithorax-like (Trl) in maintaining hotspots of DNA binding throughout development. Furthermore, the data identify over 5,800 instances in which TFs target DNA regions with demonstrated enhancer activity. Regions of high TF co-occupancy are more likely to be associated with open enhancers used across cell types, while lower TF occupancy regions are associated with complex enhancers that are also regulated at the epigenetic level. A putative regulatory network generated based on these 84 regulators reveals hundreds of co-binding events, thousands of potential regulatory interactions, and distinct regulatory strategies at developmental and housekeeping genes. These data serve as a resource for the research community in the continued effort to dissect transcriptional regulatory mechanisms directing Drosophila development. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf This is a dataset generated by the Drosophila Regulatory Elements modENCODE Project led by Kevin P. White at the University of Chicago.

Dataset Information

A draft map of cis-regulatory sequences in the mouse genome [ChIP-Seq]

Publications

A map of the cis-regulatory sequences in the mouse genome.

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