著者

有吉 眞理子 白川 昌宏

出版者

一般社団法人 日本生物物理学会

雑誌

生物物理 (ISSN:05824052)

巻号頁・発行日

vol.51, no.3, pp.124-127, 2011 (Released:2011-05-25)

参考文献数

19

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DNA methylation is a heritable epigenetic mark that enables the tissue-specific gene expression accompanied by modulation of chromatin structure. Interpretation and maintenance of DNA methylation pattern on genome are crucial for a wide range of biological processes such as genomic imprinting, embryogenesis and carcinogenesis. Recent crystallographic studies of methylated DNA binding proteins have provided a new insight into the molecular mechanisms underlying epigenetic regulation. This review focuses on a structure basis for strict recognition of the methylation status of the CpG site by DNA binding domains in MBD family proteins and UHRF1.

著者

有吉 眞理子 大谷 淳二 白川 昌宏

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.1, pp.3-9, 2015-01-01 (Released:2015-01-01)

参考文献数

17

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DNA methylation is one of the major epigenetic marks in the mammalian genome to define chromatin higher-order structure, and plays essential roles in various developmental processes. In the mammalian genome, DNA methylation mainly occurs at the 5th position of cytosine bases in a palindromic 5′-CG-3′dinucleotide sequence. Methyl CpG binding domain (MBD) proteins recognize symmetrically methylated CpG sites (5mCG/5mCG) through a conserved MBD, and recruit transcriptional repressors or chromatin modifiers. One of the MBD proteins, MBD4, uniquely contains a C-terminal glycosylation domain together with an N-terminal MBD, and functions as a mismatch DNA repair enzyme specific for T/G or U/G mismatch bases generated by spontaneous deamination of 5-methylcytosine. The base excision activity of MBD4 is also implicated in active DNA demethylation initiated by the conversion of 5-methylcytosine to thymine by deaminases. Unlike other MBD proteins, MBD4 recognizes not only 5mCG/5mCG but also T/G mismatched sites generated by spontaneous deamination of 5-methylcytosine (5mCG/TG). In addition, our biochemical data demonstrate that MBD also binds to intermediates in DNA demethylation pathways, such as 5-hydroxymethyl-cytosine (hmC), 5-carboxyl-cytosine and 5-hydroxy-uracil. The crystal structures of MBDMBD4 in complex with 5mCG/TG, 5mCG/5mCG or 5mCG/hmCG provide new structural insights into the versatility of base recognition by MBD4. A DNA interface of MBD4 has flexible structural features, in which an extensive hydration water network supports the versatile base specificity of MBD4. The versatile base recognition by MBDMBD4 implies multi-functional roles of MBD4 in the regulation of dynamic DNA methylation patterns.

著者

五十嵐 龍治 白川 昌宏

出版者

学研メディカル秀潤社 ; 1982-

雑誌

細胞工学 (ISSN:02873796)

巻号頁・発行日

vol.33, no.8, pp.850-855, 2014