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During mammalian development, it is essential that the proper epigenetic state is established across the entire genome in each differentiated cell. To date, little is known about the mechanism for establishing epigenetic modi-fications of individual genes during the course of cellular differentiation. | ễFEBS Journal MINIREVIEW Epigenetics the study of embryonic stem cells by restriction landmark genomic scanning Naka Hattori and Kunio Shiota Laboratory of Cellular Biochemistry AnimalResource Sciences Veterinary MedicalSciences University of Tokyo Japan Keywords DNA methylation DNA methylation profile Dnmt epigenetics ES cells histone methylase histone modification mammalian development RLGS T-DMR During mammalian development it is essential that the proper epigenetic state is established across the entire genome in each differentiated cell. To date little is known about the mechanism for establishing epigenetic modifications of individual genes during the course of cellular differentiation. Genome-wide DNA methylation analysis of embryonic stem cells by Correspondence N. Hattori Institute of Life Sciences Ajinomoto Co. Inc. 1-1 Suzuki-cho Kawasaki-ku Kawasaki-shi 210-8681 Japan Fax 81 44 244 9617 Tel 81 44 210 5959 E-mail naka_hattori@ajinomoto.com restriction landmark genomic scanning provides information about cell type- and tissue-specific DNA methylation profiles at tissue-specific methylated regions associated with developmental processes. It also sheds light on DNA methylation alterations following fetal exposure to chemical agents. In addition analysis of embryonic stem cells deficient in epigenetic regulators will contribute to revealing the mechanism for establishing DNA methylation profiles and the interplay between DNA methylation and other Present address Institute of Life Sciences Ajinomoto Co. Inc. Japan epigenetic modifications. Received 30 November 2007 revised 25 January 2008 accepted 29 January 2008 doi 10.1111 j.1742-4658.2008.06331.x Differentiation of a specific cell type involves the establishment of a precise epigenetic profile comprised of genome-wide epigenetic modifications such as DNA methylation and histone modification. Because epigenetic modifications in gene areas regulate transcriptional activity the epigenetic profile of the cell