Comprehensive nucleosome mapping of the human genome in cancer progression

Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Several important studies have mapped human nucleosome distributions genome wide, but the genome-wide role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Sequence Capture method, mTSS-seq, to map genome-wide nucleosome distribution 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. Nucleosome distribution mapping in primary patient tissue at all transcription start sites in the human genome Please note that two processed data files '4137N_ALLcombined.bed' and '4137T_ALLcombined.bed' (linked as Series supplementary file) are processed bed files combined from three 4137N_*_hiseq samples (total 6 raw data files) and three 4137T_*_hiseq samples (total 6 raw data files), respectively.