Influence of DNA methylation on positioning and DNA flexibility of nucleosomes with pericentric satellite DNA

被引：20

作者：

Osakabe, Akihisa ^{[1
]}

Adachi, Fumiya ^{[1
]}

Arimura, Yasuhiro ^{[1
]}

Maehara, Kazumitsu ^{[2
]}

Ohkawa, Yasuyuki ^{[2
]}

Kurumizaka, Hitoshi ^{[1
]}

机构：

[1] Waseda Univ, Struct Biol Lab, Grad Sch Adv Sci & Engn, Shinjuku Ku, Tokyo 1628480, Japan

[2] Kyushu Univ, Fac Med, Dept Adv Med Initiat, Fukuoka 8128582, Japan

来源：

OPEN BIOLOGY | 2015年 / 5卷 / 10期

关键词：

chromatin; nucleosome; pericentric heterochromatin; DNA methylation; CRYSTAL-STRUCTURE; CPG-ISLANDS; BINDING PROTEINS; CORE PARTICLE; CANCER; HYPOMETHYLATION; EXPRESSION; COMPACTION; STABILITY; CHROMATIN;

D O I：

10.1098/rsob.150128

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA methylation occurs on CpG sites and is important to form pericentric heterochromatin domains. The satellite 2 sequence, containing seven CpG sites, is located in the pericentric region of human chromosome 1 and is highly methylated in normal cells. In contrast, the satellite 2 region is reportedly hypomethylated in cancer cells, suggesting that the methylation status may affect the chromatin structure around the pericentric regions in tumours. In this study, we mapped the nucleosome positioning on the satellite 2 sequence in vitro and found that DNA methylation modestly affects the distribution of the nucleosome positioning. The micrococcal nuclease assay revealed that the DNA end flexibility of the nucleosomes changes, depending on the DNA methylation status. However, the structures and thermal stabilities of the nucleosomes are unaffected by DNA methylation. These findings provide new information to understand how DNA methylation functions in regulating pericentric heterochromatin formation and maintenance in normal and malignant cells.

引用

页数：9

共 49 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2] Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3 [J].

Arimura, Yasuhiro ;

Shirayama, Kazuyoshi ;

Horikoshi, Naoki ;

Fujita, Risa ;

Taguchi, Hiroyuki ;

Kagawa, Wataru ;

Fukagawa, Tatsuo ;

Almouzni, Genevieve ;

Kurumizaka, Hitoshi .

SCIENTIFIC REPORTS, 2014, 4

[3] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[4] Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? [J].

Baylin, SB ;

Ohm, JE .

NATURE REVIEWS CANCER, 2006, 6 (02) :107-116

[5] DNA methylation and gene silencing in cancer [J].

Baylin S.B. .

Nature Clinical Practice Oncology, 2005, 2 (Suppl 1) :S4-S11

[6] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[7] Relationship between nucleosome positioning and DNA methylation [J].

Chodavarapu, Ramakrishna K. ;

Feng, Suhua ;

Bernatavichute, Yana V. ;

Chen, Pao-Yang ;

Stroud, Hume ;

Yu, Yanchun ;

Hetzel, Jonathan A. ;

Kuo, Frank ;

Kim, Jin ;

Cokus, Shawn J. ;

Casero, David ;

Bernal, Maria ;

Huijser, Peter ;

Clark, Amander T. ;

Kraemer, Ute ;

Merchant, Sabeeha S. ;

Zhang, Xiaoyu ;

Jacobsen, Steven E. ;

Pellegrini, Matteo .

NATURE, 2010, 466 (7304) :388-392

[8] DNA Methylation Increases Nucleosome Compaction and Rigidity [J].

Choy, John S. ;

Wei, Sijie ;

Lee, Ju Yeon ;

Tan, Song ;

Chu, Steven ;

Lee, Tae-Hee .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (06) :1782-+

[9] The mechanics behind DNA sequence-dependent properties of the nucleosome [J].

Chua, Eugene Y. D. ;

Vasudevan, Dileep ;

Davey, Gabriela E. ;

Wu, Bin ;

Davey, Curt A. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (13) :6338-6352

[10] Effects of DNA methylation on nucleosome stability [J].

Collings, Clayton K. ;

Waddell, Peter J. ;

Anderson, John N. .

NUCLEIC ACIDS RESEARCH, 2013, 41 (05) :2918-2931

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