PT  - JOURNAL ARTICLE
AU  - John F. Fullard
AU  - Claudia Giambartolomei
AU  - Mads E. Hauberg
AU  - Ke Xu
AU  - Christopher Bare
AU  - Joel T. Dudley
AU  - Manuel Mattheisen
AU  - Joseph K. Pickrell
AU  - Vahram Haroutunian
AU  - Panos Roussos
TI  - Cell-type specific open chromatin profiling in human postmortem brain infers functional roles for non-coding schizophrenia loci
AID  - 10.1101/062513
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 062513
4099  - http://biorxiv.org/content/early/2016/07/07/062513.short
4100  - http://biorxiv.org/content/early/2016/07/07/062513.full
AB  - To better understand the role of cis regulatory elements in neuropsychiatric disorders we applied ATAC-seq to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain. Most of the identified open chromatin regions (OCRs) are differentially accessible between neurons and non-neurons, and show enrichment with known cell type markers, promoters and enhancers. Relative to those of non-neurons, neuronal OCRs are more evolutionarily conserved and are enriched in distal regulatory elements. Our data reveals sex differences in chromatin accessibility and identifies novel OCRs that escape X chromosome inactivation, with implications for intellectual disability. Transcription factor footprinting analysis identifies differences in the regulome between neuronal and non-neuronal cells and ascribes putative functional roles to 16 non-coding schizophrenia risk variants. These results represent the first analysis of cell-type-specific OCRs and TF binding sites in postmortem human brain and further our understanding of the regulome and the impact of neuropsychiatric disease-associated genetic risk variants.