RT Journal Article
SR Electronic
T1 Chromatin co-accessibility is highly structured, spans entire chromosomes, and mediates long range regulatory genetic effects
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 604371
DO 10.1101/604371
A1 William W. Young Greenwald
A1 Agnieszka D’Antonio-Chronowska
A1 Paola Benaglio
A1 Hiroko Matsui
A1 Erin N. Smith
A1 Matteo D’Antonio
A1 Kelly A. Frazer
YR 2019
UL http://biorxiv.org/content/early/2019/04/09/604371.abstract
AB Chromatin accessibility identifies active regions of the genome, often at transcription factor (TF) binding sites, enhancers, and promoters, and contains regulatory genetic variation. Functionally related accessible sites have been reported to be co-accessible; however, the prevalence and range of co-accessibility is unknown. We perform ATAC-seq in induced pluripotent stem cells from 134 individuals and integrate it with RNA-seq, WGS, and ChIP-seq, providing the first long-range chromosome-length analysis of co-accessibility. We show that co-accessibility is highly connected, with sites having a median of 24 co-accessible partners up to 250Mb away. We also show that co-accessibility can de novo identify known and novel co-expressed genes, and co-regulatory TFs and chromatin states. We perform a cis and trans-caQTL, a trans-eQTL, and examine allelic effects of co-accessibility, identifying tens of thousands of trans-caQTLs, and showing that trans genetic effects can be propagated through co-accessibility to gene expression for cell-type and disease relevant genes.