Unknown,Transcriptomics,Genomics,Proteomics

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Regional Differences in gene expression and promoter usage in aged human brains

ABSTRACT: Cap analysis of gene expression (CAGE) and massive parallel sequencing were used to profile the promoterome of aged human brains from five regions, namely: caudate, frontal cortex, hippocampus, putamen and temporal cortex. 25 RNA libraries from post-mortem brain tissue (five caudate, five frontal, 5 hippocampus, 5 putamen, five temporal RNA libraries from seven individuals) were processed using CAGE protocol and CAGE tags derived from the 25 libraries were sequenced with Illumina.

ORGANISM(S): Homo sapiens

SUBMITTER: Luba Pardo

PROVIDER: E-GEOD-43472 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Genome-wide mapping of transcriptional regulatory elements are essential tools for the understanding of the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of nascent, Pol-II-transcribed RNAs by Cap Analysis of Gene Expression (CAGE-Seq) with genome-wide profiling of histones modifications by chromatin immunoprecipitation (ChIP-seq) to map active promoters and enhancers in a model of human neural commitment, represented by embryonic stem cells (ESCs) induced to differentiate into self-renewing neuroepithelial-like stem cells (NESC). We integrated CAGE-seq, ChIP-seq and gene expression profiles to discover shared or cell-specific regulatory elements, transcription start sites and transcripts associated to the transition from pluripotent to neural-restricted stem cell. Our analysis showed that >90% of the promoters are in common between the two cell types, while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a “bivalent” histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provide a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and gene expression programs occurring in the transition from a pluripotent to a neural-restricted cell fate. Investiagtion of promoters usage changes during ESCs neural induction ESCs and NESCs promoter usage profiling by CAGE-seq

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Regional Differences in gene expression and promoter usage in aged human brains

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