Oncotarget

Research Papers: Chromosome:

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 and Jonathan H. Dennis _

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Oncotarget. 2016; 7:13429-13445. https://doi.org/10.18632/oncotarget.6811

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Abstract

Brooke R. Druliner1,5, Daniel Vera1,6, Ruth Johnson2, Xiaoyang Ruan3, Lynn M. Apone4, Eileen T. Dimalanta4, Fiona J. Stewart4, Lisa Boardman5 and Jonathan H. Dennis1,6,7

1 Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America

2 Department of Laboratory Medicine and Experimental Pathology, Mayo Clinic, Rochester, Minnesota, United States of America

3 Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America

4 New England Biolabs Inc., Ipswich, Massachusetts, United States of America

5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America

6 The Center for Genomics and Personalized Medicine, The Florida State University, Tallahassee, Florida, United States of America

7 Institute of Molecular Biophysics, The Florida State University, Tallahassee, Florida, United States of America

Correspondence to:

Jonathan H. Dennis, email:

Keywords: cancer, chromatin, nucleosome, MNase, whole genome, Chromosome Section

Received: December 18, 2015 Accepted: December 21, 2015 Published: December 31, 2015

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.


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