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 Allyn Boardman, Jonathan H. Dennis

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Nucleosomes
Human Genome
Chromatin
Neoplasms
Transcription Initiation Site
Genome
Colon
Adenocarcinoma
Transcription Factors
Lung
DNA

Keywords

  • Cancer
  • Chromatin
  • Mnase
  • Nucleosome
  • Whole genome

ASJC Scopus subject areas

  • Oncology

Cite this

Druliner, B. R., Vera, D., Johnson, R., Ruan, X., Apone, L. M., Dimalanta, E. T., ... Dennis, J. H. (2016). Comprehensive nucleosome mapping of the human genome in cancer progression. Oncotarget, 7(12), 13429-13445. https://doi.org/10.18632/oncotarget.6811

Comprehensive nucleosome mapping of the human genome in cancer progression. / Druliner, Brooke R.; Vera, Daniel; Johnson, Ruth; Ruan, Xiaoyang; Apone, Lynn M.; Dimalanta, Eileen T.; Stewart, Fiona J.; Boardman, Lisa Allyn; Dennis, Jonathan H.

In: Oncotarget, Vol. 7, No. 12, 22.03.2016, p. 13429-13445.

Research output: Contribution to journalArticle

Druliner, BR, Vera, D, Johnson, R, Ruan, X, Apone, LM, Dimalanta, ET, Stewart, FJ, Boardman, LA & Dennis, JH 2016, 'Comprehensive nucleosome mapping of the human genome in cancer progression', Oncotarget, vol. 7, no. 12, pp. 13429-13445. https://doi.org/10.18632/oncotarget.6811
Druliner BR, Vera D, Johnson R, Ruan X, Apone LM, Dimalanta ET et al. Comprehensive nucleosome mapping of the human genome in cancer progression. Oncotarget. 2016 Mar 22;7(12):13429-13445. https://doi.org/10.18632/oncotarget.6811
Druliner, Brooke R. ; Vera, Daniel ; Johnson, Ruth ; Ruan, Xiaoyang ; Apone, Lynn M. ; Dimalanta, Eileen T. ; Stewart, Fiona J. ; Boardman, Lisa Allyn ; Dennis, Jonathan H. / Comprehensive nucleosome mapping of the human genome in cancer progression. In: Oncotarget. 2016 ; Vol. 7, No. 12. pp. 13429-13445.
@article{2d422b32243e4f8d9854373b8286aead,
title = "Comprehensive nucleosome mapping of the human genome in cancer progression",
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.",
keywords = "Cancer, Chromatin, Mnase, Nucleosome, Whole genome",
author = "Druliner, {Brooke R.} and Daniel Vera and Ruth Johnson and Xiaoyang Ruan and Apone, {Lynn M.} and Dimalanta, {Eileen T.} and Stewart, {Fiona J.} and Boardman, {Lisa Allyn} and Dennis, {Jonathan H.}",
year = "2016",
month = "3",
day = "22",
doi = "10.18632/oncotarget.6811",
language = "English (US)",
volume = "7",
pages = "13429--13445",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "12",

}

TY - JOUR

T1 - Comprehensive nucleosome mapping of the human genome in cancer progression

AU - Druliner, Brooke R.

AU - Vera, Daniel

AU - Johnson, Ruth

AU - Ruan, Xiaoyang

AU - Apone, Lynn M.

AU - Dimalanta, Eileen T.

AU - Stewart, Fiona J.

AU - Boardman, Lisa Allyn

AU - Dennis, Jonathan H.

PY - 2016/3/22

Y1 - 2016/3/22

N2 - 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.

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.

KW - Cancer

KW - Chromatin

KW - Mnase

KW - Nucleosome

KW - Whole genome

UR - http://www.scopus.com/inward/record.url?scp=84971634538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84971634538&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.6811

DO - 10.18632/oncotarget.6811

M3 - Article

C2 - 26735342

AN - SCOPUS:84971634538

VL - 7

SP - 13429

EP - 13445

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 12

ER -