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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13429-13445
Number of pages17
JournalOncotarget
Volume7
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • Cancer
  • Chromatin
  • Mnase
  • Nucleosome
  • Whole genome

ASJC Scopus subject areas

  • Oncology

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