Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation

Suhn K. Rhie, Shannon Schreiner, Heather Witt, Chris Armoskus, Fides D. Lay, Adrian Camarena, Valeria N. Spitsyna, Yu Guo, Benjamin P. Berman, Oleg V. Evgrafov, James A. Knowles, Peggy J. Farnham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

As part of PsychENCODE, we developed a three-dimensional (3D) epigenomic map of primary cultured neuronal cells derived from olfactory neuroepithelium (CNON). We mapped topologically associating domains and high-resolution chromatin interactions using Hi-C and identified regulatory elements using chromatin immunoprecipitation and nucleosome positioning assays. Using epigenomic datasets from biopsies of 63 living individuals, we found that epigenetic marks at distal regulatory elements are more variable than marks at proximal regulatory elements. By integrating genotype and metadata, we identified enhancers that have different levels corresponding to differences in genetic variation, gender, smoking, and schizophrenia. Motif searches revealed that many CNON enhancers are bound by neuronal-related transcription factors. Last, we combined 3D epigenomic maps and gene expression profiles to predict enhancer-target gene interactions on a genome-wide scale. This study not only provides a framework for understanding individual epigenetic variation using a primary cell model system but also contributes valuable data resources for epigenomic studies of neuronal epithelium.

Original languageAmerican English
Article numbereaav8550
JournalScience advances
Volume4
Issue number12
DOIs
StatePublished - 13 Dec 2018
Externally publishedYes

Bibliographical note

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Copyright © 2018 The Authors, some rights reserved.

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