Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation.
Suhn Kyong RhieShannon M SchreinerHeather WittChris ArmoskusFides D LayAdrian CamarenaValeria N SpitsynaYu GuoBenjamin P BermanOleg V EvgrafovJames A KnowlesPeggy J FarnhamPublished in: Science advances (2018)
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.
Keyphrases
- transcription factor
- genome wide
- dna methylation
- genome wide identification
- gene expression
- high resolution
- copy number
- cerebral ischemia
- single cell
- dna binding
- dna damage
- stem cells
- endothelial cells
- high throughput
- electronic health record
- machine learning
- mental health
- blood brain barrier
- rna seq
- cell cycle arrest
- big data
- deep learning
- smoking cessation
- subarachnoid hemorrhage
- binding protein
- liquid chromatography
- high density
- signaling pathway
- artificial intelligence
- genome wide analysis