A draft map of cis-regulatory sequences in the mouse genome [RNA-Seq]
Ontology highlight
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.
Project description: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.
Project description: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. Cortex Hi-C experiment were conducted in biological replicates
Project description: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.
Project description: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.
Project description: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.
Project description:The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 billion bases of the mouse genome share 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. To date, 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 has been a powerful tool for the discovery of these sequences, but it alone cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including human, D. melanogaster and C. elegans. We have applied the same experimental approach to a diverse set of 19 tissues and cell types in the mouse, producing a map of nearly 300,000 murine cis-regulatory sequences. This map provides functional annotation to nearly 11% of the mouse genome, and over 70% of conserved, non-coding sequences (CNS). We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we demonstrate that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and study of mechanisms regulating tissue-specific gene expression. This SuperSeries is composed of the SubSeries listed below.
Project description:Bread wheat is allohexaploid with 16 Gb genome, which has large intergenic region with abundant TEs and regulatory sequences . Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide the first systematic epigenomic map for functional annotation of the allohexaploid wheat genome.
Project description:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.
Project description:Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs), enhancers and silencers. While enhancers have been thoroughly characterized, the properties and mechansisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs, as they mostly lack detectable DNA accessibility. The silencer-binding TF CG11247, which we term Saft, safeguards cell fate decisions in vivo and functions via a highly-conserved domain we term ZAC and the corepressor G9a, independently of G9a’s H3K9-methyltransferase activity. Overall, our identification of silencers with unexpected properties and mechanisms has important implications for the understanding and future study of repressive CREs, as well as the functional annotation of animal genomes.
Project description:The zebrafish has been widely used for the study of human disease and development, as ~70% of the protein-coding genes are conserved between the two species. Annotation of functional control elements of the zebrafish genome, however, has lagged behind that of other model systems such as mouse and Drosophila. Based on multi-omics approaches taken in the ENCODE and Roadmap Epigenomics projects, we performed RNA-seq, ATAC-seq, ChIP-seq and Hi-C experiments in ten adult and two embryonic tissues to generate a comprehensive map of transcriptomes and regulatory elements in the zebrafish Tuebingen reference strain. Overall, we have identified 235,596 cis-regulatory elements, which potentially shape the tissue-specific and developmental-stage-specific gene expression in zebrafish. A comparison of zebrafish, human, and mouse regulatory elements allowed us to identify both evolutionarily conserved and species-specific regulatory sequences. Furthermore, through the analysis of Hi-C data in zebrafish brain and muscle, we observed different levels of 3D genome organization, including compartment, topological associating domains (TADs), and chromatin loops in zebrafish. A subset of TADs are deeply conserved between zebrafish and human. This work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionally conserved elements of 3D genome organization.