Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A High-Resolution Enhancer Atlas of the Developing Telencephalon

ABSTRACT: The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant‐acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web‐based enhancer atlas comprising over 33,000 sections. We show how this large collection of annotated telencephalon enhancers can be used to study the regulatory architecture of individual genes, to examine the sequence motif content of enhancers, and to drive targeted reporter or effector protein expression in experimental applications. Furthermore, we used epigenomic analysis of human and mouse cortex tissue to directly compare the genome‐wide enhancer architecture in these species. This atlas provides a primary resource for investigating gene regulatory mechanisms of telencephalon development and enables studies of the role of distant‐acting enhancers in neurodevelopmental disorders. Examination of p300 binding in mouse embryonic stage 11.5 forebrain, mouse postnatal (P0) cortex tissue and human fetal (gestational week 20) cortex

ORGANISM(S): Homo sapiens

SUBMITTER: Matthew Blow

PROVIDER: E-GEOD-42881 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:While the majority of protein-coding genes in the human genome have been identified, the location of the regulatory sequences that control their expression in time and space remains poorly defined. The importance of identifying these elements is underscored by a growing number of studies (such as GWAS) supporting a relationship between variation in non-coding sequences and human disease. M-BM- emonstrated that ChIP-Seq with p300 directly on human or mouse tissues represents a powerful method to identify the location and tissue-specific activity pattern of enhancers in the genome.M-BM- a highly specific chromatin mark for the prediction of in vivo enhancers, it is not without limitations. M-BM- comparison of p300-bound regions with previously generated enhancer sets shows that the majority of enhancers are activated independently of p300. To attempt to identify a larger proportion of enhancers in vivo, we have focused on several additional transcriptional coactivators that are hypothesized to be associated with active tissue-specific enhancers. M-BM- limited availability of ChIP-seq grade antibodies for these coactivators, FLAG-tag knock-in mice were generated and ChIP-seq using a FLAG antibody was performed on various tissues from e11.5 mouse embryos. Indeed, as these mouse lines have become available we have validated their valuable role as marks for transcriptional enhancers in vivo.M-BM- studies are expected to further expand the catalogue of in vivo functional enhancers, which will aid in the decoding of the regulatory genome and provide new insights into the role of gene regulation in human biology and disease. In addition to FLAG data, this accession includes histone acetylation / methylation ChIP-seq data from e11.5 mouse embryonic tissues. Histone ChIP-seq data was used in combination with FLAG data for various computational analyses. Examination of FLAG-labeled transcriptional coactivator binding in mouse embryonic stage 11.5 and embryonic stem cells

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A High-Resolution Enhancer Atlas of the Developing Telencephalon

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