Comprehensive nucleosome mapping of the human genome in cancer progression

Brooke R. Druliner, Daniel Vera, Ruth Johnson, Xiaoyang Ruan, Lynn M. Apone, Eileen T. Dimalanta, Fiona J. Stewart, Lisa Boardman, Jonathan H. Dennis
2015 OncoTarget  
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
more » ... 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 DNAdirected nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation.
doi:10.18632/oncotarget.6811 pmid:26735342 pmcid:PMC4924652 fatcat:alfx3fc26fh4raohuuahs4xgdu