Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues

Gilad Landan, Netta Mendelson Cohen, Zohar Mukamel, Amir Bar, Alina Molchadsky, Ran Brosh, Shirley Horn-Saban, Daniela Amann Zalcenstein, Naomi Goldfinger, Adi Zundelevich, Einav Nili Gal-Yam, Varda Rotter, Amos Tanay

Research output: Contribution to journalArticle

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Abstract

DNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. Here, we show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using in vitro evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average. The data indicate that changes in population-averaged methylation occur through a stochastic process that generates a stream of local and uncorrelated methylation aberrations. Despite the stochastic nature of the process, nearly deterministic epigenetic remodeling emerges on average at loci that lose or gain resistance to methylation accumulation. Changes in the susceptibility to methylation accumulation are correlated with changes in histone modification and CTCF occupancy. Characterizing epigenomic polymorphism within cell populations is therefore critical to understanding methylation dynamics in normal and cancer cells.

Original languageEnglish (US)
Pages (from-to)1207-1214
Number of pages8
JournalNature Genetics
Volume44
Issue number11
DOIs
StatePublished - Nov 1 2012

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Epigenomics
Methylation
Stochastic Processes
Histone Code
Population
DNA Methylation
Neoplasms
Fibroblasts

ASJC Scopus subject areas

  • Genetics

Cite this

Landan, G., Cohen, N. M., Mukamel, Z., Bar, A., Molchadsky, A., Brosh, R., ... Tanay, A. (2012). Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nature Genetics, 44(11), 1207-1214. https://doi.org/10.1038/ng.2442

Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. / Landan, Gilad; Cohen, Netta Mendelson; Mukamel, Zohar; Bar, Amir; Molchadsky, Alina; Brosh, Ran; Horn-Saban, Shirley; Zalcenstein, Daniela Amann; Goldfinger, Naomi; Zundelevich, Adi; Nili Gal-Yam, Einav; Rotter, Varda; Tanay, Amos.

In: Nature Genetics, Vol. 44, No. 11, 01.11.2012, p. 1207-1214.

Research output: Contribution to journalArticle

Landan, G, Cohen, NM, Mukamel, Z, Bar, A, Molchadsky, A, Brosh, R, Horn-Saban, S, Zalcenstein, DA, Goldfinger, N, Zundelevich, A, Nili Gal-Yam, E, Rotter, V & Tanay, A 2012, 'Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues', Nature Genetics, vol. 44, no. 11, pp. 1207-1214. https://doi.org/10.1038/ng.2442
Landan, Gilad ; Cohen, Netta Mendelson ; Mukamel, Zohar ; Bar, Amir ; Molchadsky, Alina ; Brosh, Ran ; Horn-Saban, Shirley ; Zalcenstein, Daniela Amann ; Goldfinger, Naomi ; Zundelevich, Adi ; Nili Gal-Yam, Einav ; Rotter, Varda ; Tanay, Amos. / Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. In: Nature Genetics. 2012 ; Vol. 44, No. 11. pp. 1207-1214.
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