Single sample sequencing (S3EQ) of epigenome and transcriptome in nucleus accumbens

Journal of Neuroscience Methods
S J Xu, Elizabeth A Heller

Abstract

High-throughput sequencing has been widely applied to uncover the molecular mechanisms underlying neurological and psychiatric disorders. The large body of data support the role of epigenetic mechanisms in neurological function of both human and animals. Yet, the existing data is limited by the fact that epigenetic and transcriptomic changes have only been measured in separate cohorts. This has limited precise correlation of epigenetic changes in gene expression. Single Sample Sequencing (S3EQ) is an innovative approach to analyze both epigenetic and transcriptomic regulation within a single neuronal sample. Using this method, we analyzed chromatin immunoprecipitation (ChIP)- and RNA-sequencing data from the nucleus accumbens (NAc) of the same animal. ChIP-S3EQ of neuronal nuclei reliably identified hPTM enrichment in the adult mouse NAc with high precision. Comparing cellular compartments, we found that the spliceosome of whole cell RNA-seq was more closely recapitulated by cytosolic RNA-S3EQ than nuclear RNA-seq. Finally, S3EQ showed increased sensitivity for correlating chromatin modifications with gene expression, especially for lowly expressed transcripts. S3EQ accurately generates both RNA- and ChIP-seq from a single samp...Continue Reading

Citations

Jan 26, 2020·Nature Communications·Marco D CarpenterElizabeth A Heller

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