Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island

Joy C. Lin, Shinwu Jeong, Gangning Liang, Daiya Takai, Merhnaz Fatemi, Yvonne C. Tsai, Gerda Egger, Einav Nili Gal-Yam, Peter A. Jones

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Epigenetic silencing of tumor suppressor genes is generally thought to involve DNA cytosine methylation, covalent modifications of histones, and chromatin compaction. Here, we show that silencing of the three transcription start sites in the bidirectional MLH1 promoter CpG island in cancer cells involves distinct changes in nucleosomal occupancy. Three nucleosomes, almost completely absent from the start sites in normal cells, are present on the methylated and silenced promoter, suggesting that epigenetic silencing may be accomplished by the stable placement of nucleosomes into previously vacant positions. Activation of the promoter by demethylation with 5-aza-2′-deoxycytidine involves nucleosome eviction. Epigenetic silencing of tumor suppressor genes may involve heritable changes in nucleosome occupancy enabled by cytosine methylation.

Original languageEnglish (US)
Pages (from-to)432-444
Number of pages13
JournalCancer cell
Volume12
Issue number5
DOIs
StatePublished - Nov 13 2007

Fingerprint

CpG Islands
Nucleosomes
Epigenomics
Cytosine
decitabine
Tumor Suppressor Genes
Histone Code
Transcription Initiation Site
DNA Methylation
Methylation
Chromatin
Neoplasms

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Lin, J. C., Jeong, S., Liang, G., Takai, D., Fatemi, M., Tsai, Y. C., ... Jones, P. A. (2007). Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island. Cancer cell, 12(5), 432-444. https://doi.org/10.1016/j.ccr.2007.10.014

Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island. / Lin, Joy C.; Jeong, Shinwu; Liang, Gangning; Takai, Daiya; Fatemi, Merhnaz; Tsai, Yvonne C.; Egger, Gerda; Gal-Yam, Einav Nili; Jones, Peter A.

In: Cancer cell, Vol. 12, No. 5, 13.11.2007, p. 432-444.

Research output: Contribution to journalArticle

Lin, JC, Jeong, S, Liang, G, Takai, D, Fatemi, M, Tsai, YC, Egger, G, Gal-Yam, EN & Jones, PA 2007, 'Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island', Cancer cell, vol. 12, no. 5, pp. 432-444. https://doi.org/10.1016/j.ccr.2007.10.014
Lin JC, Jeong S, Liang G, Takai D, Fatemi M, Tsai YC et al. Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island. Cancer cell. 2007 Nov 13;12(5):432-444. https://doi.org/10.1016/j.ccr.2007.10.014
Lin, Joy C. ; Jeong, Shinwu ; Liang, Gangning ; Takai, Daiya ; Fatemi, Merhnaz ; Tsai, Yvonne C. ; Egger, Gerda ; Gal-Yam, Einav Nili ; Jones, Peter A. / Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island. In: Cancer cell. 2007 ; Vol. 12, No. 5. pp. 432-444.
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