Cell-free DNA comprises an in vivo, genome-wide nucleosome footprint that informs its tissue(s)-of-origin

ABSTRACT: Nucleosomes are the basic unit of packaging of eukaryotic chromatin, and nucleosome positioning can differ substantially between cell types. Here, we sequence 14.5 billion plasma-borne cell-free DNA (cfDNA) fragments (700-fold coverage) to generate genome-wide maps of in vivo nucleosome occupancy. We identify 13 million local maxima of nucleosome protection, spanning 2.53 gigabases (Gb) of the human genome, whose positions and spacings correlate with nuclear architecture, gene structure and gene expression. We further show that short cfDNA fragments - poorly recovered by standard protocols - directly footprint the in vivo occupancy of DNA-bound transcription factors such as CTCF. The sequence composition of cfDNA has previously been used to noninvasively monitor cancer, pregnancy and organ

ORGANISM(S): Homo sapiens

SUBMITTER: Jay Shendure 

PROVIDER: E-GEOD-71378 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress