RT Journal Article
SR Electronic
T1 Cell-type specific open chromatin profiling in human postmortem brain infers functional roles for non-coding schizophrenia loci
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 062513
DO 10.1101/062513
A1 John F. Fullard
A1 Claudia Giambartolomei
A1 Mads E. Hauberg
A1 Ke Xu
A1 Christopher Bare
A1 Joel T. Dudley
A1 Manuel Mattheisen
A1 Joseph K. Pickrell
A1 Vahram Haroutunian
A1 Panos Roussos
YR 2016
UL http://biorxiv.org/content/early/2016/07/07/062513.abstract
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.