RT Journal Article SR Electronic T1 Comprehensive nucleosome mapping of the human genome in cancer progression JF bioRxiv FD Cold Spring Harbor Laboratory SP 021618 DO 10.1101/021618 A1 Brooke R. Druliner A1 Daniel Vera A1 Ruth Johnson A1 Xiaoyang Ruan A1 Lynne M. Apone A1 Eileen T. Dimalanta A1 Fiona J. Stewart A1 Lisa Boardman A1 Jonathan H. Dennis YR 2015 UL http://biorxiv.org/content/early/2015/06/27/021618.abstract AB Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation.Significance This is the first report of human nucleosome distribution in cancer progression using sequence capture and HiSeq. We show in lung and colorectal adenocarcinoma patients that nucleosome distribution is a widespread, early response driven by genetically-encoded signals and potentiate regulatory factor binding. We present a model for chromatin-based hierarchical regulation.