The International Journal of Developmental Biology

Int. J. Dev. Biol. 53: 203 - 214 (2009)

Vol 53, Issue 2-3

Special Issue: Epigenetics & Development

Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development

Review | Published: 28 April 2009

Kohta Ikegami1, Jun Ohgane1, Satoshi Tanaka1, Shintaro Yagi1, and Kunio Shiota*,1,2

1Laboratory of Cellular Biochemistry, Animal Resource Sciences / Veterinary Medical Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo and 2Organ Development Research Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba-city, Japan


Genes constitute only a small proportion of the mammalian genome, the majority of which is composed of non-genic repetitive elements including interspersed repeats and satellites. A unique feature of the mammalian genome is that there are numerous tissue-dependent, differentially methylated regions (T-DMRs) in the non-repetitive sequences, which include genes and their regulatory elements. The epigenetic status of T-DMRs varies from that of repetitive elements and constitutes the DNA methylation profile genome-wide. Since the DNA methylation profile is specific to each cell and tissue type, much like a fingerprint, it can be used as a means of identification. The formation of DNA methylation profiles is the basis for cell differentiation and development in mammals. The epigenetic status of each T-DMR is regulated by the interplay between DNA methyltransferases, histone modification enzymes, histone subtypes, non-histone nuclear proteins and non-coding RNAs. In this review, we will discuss how these epigenetic factors cooperate to establish cell- and tissue-specific DNA methylation profiles.


epigenetics, DNA methylation, T-DMR, histone modification, chromatin remodeling

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