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Stem Cells and Cancer pp 85–97Cite as

Stem Cell Chromatin Patterns and DNA Hypermethylation

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Normal development requires carefully orchestrated cellular remodeling on both a global and gene-specific/tissue-specific level. Heritable changes in gene expression that occur independently of alterations in the primary DNA sequence are deemed “epigenetic,” and are largely characterized by a tightly regulated program of active and repressive histone modifications. In this chapter, we will discuss the histone modifications that help modulate gene expression during development, as well as the normal stem/progenitor cell epigenetic remodeling proteins, including polycomb group (PcG) proteins, which control these modifications. Intriguingly, the methylation of CpG dinucleotides in DNA also plays a critical role during both normal and malignant epigenetic reprogramming. DNA methylation is a critical mediator of both X-chromosome inactivation and paternal and maternal imprinting, the variable regulation of tissue/cell specific activation of genes required for successful differentiation of alternate cell lineages, and the permanent silencing of genes required for stem/progenitor cell maintenance and pluripotency. Aberrant DNA methylation is a key component of the malignant epigenetic programs that are pervasive in all types of cancer and are thought to contribute to tumor initiation and progression. The clustering of silenced genes within single cell pathways and the remarkable frequency with which epigenetically silenced genes are being identified within any given cancer type begs the question of whether gene silencing is a series of random events resulting in an enhanced survival of a premalignant clone, or whether silencing is the result of a directed, instructive program for silencing initiation reflective of the cells of origin for tumors. We hypothesize that a combination of both chromatin and DNA regulatory networks controlling stem cell epigenetics may go awry in cells that give rise to tumors and during tumor progression. In this regard, the current chapter stresses the hypothesis that the malignant epigenetic program is linked, at least for silencing of some cancer genes, to the epigenetic control of stem/precursor cell gene expression patterns.

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  1. Cancer Biology Division, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, 21231, Baltimore, Maryland

    Joyce E. Ohm & Stephen B. Baylin

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  1. Joyce E. Ohm
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  2. Stephen B. Baylin
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Correspondence to Joyce E. Ohm .

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    Ohm, J.E., Baylin, S.B. (2009). Stem Cell Chromatin Patterns and DNA Hypermethylation. In: Teicher, B., Bagley, R. (eds) Stem Cells and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-933-8_7

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