臨床検査52巻6号

2008年06月発行

今月の主題 エピジェネティクスと臨床検査 総論

エピジェネティクスの制御システム

著者： 石原宏¹² 斉藤典子¹ 船原徹士¹ 中尾光善¹

所属機関： ¹熊本大学発生医学研究センター再建医学部門器官制御分野 ²熊本大学大学院先導機構

ページ範囲：P.613 - P.621

　エピジェネティクス(epigenetics)は，染色体構造の変換などによって遺伝情報が選択的かつ可逆的に活用され，それが次世代に継承される現象である．DNAのメチル基修飾，ヒストンの翻訳後修飾，クロマチンのヌクレオソーム構造，ドメイン構築，クロマチンインスレーター，さらに高次元では細胞核内構造，遺伝子の核内配置，染色体間相互作用など様々な機序がかかわる．本稿では主にDNAメチル化，ヒストンの翻訳後修飾，核内構造体因子などのエピジェネティクスの分子基盤について概説する．

参考文献

１) Strahl BD, Allis CD：The language of covalent histone modifications. Nature　403：41-45, 2000

２) Nagy Z, Tora L：Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene　26：5341-5357, 2007

３) Mujtaba S, Zeng L, Zhou MM：Structure and acetyl-lysine recognition of the bromodomain. Oncogene　26：5521-5527, 2007

４) Gregoretti IV, Lee YM, Goodson HV：Molecular evolution of the histone deacetylase family：functional implications of phylogenetic analysis. J Mol Biol　338：17-31, 2004

５) Lachner M, O'Carroll D, Rea S, et al：Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature　410：116-120, 2001

６) Bannister AJ, Zegerman P, Partridge JF, et al：Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature　410：120-124, 2001

７) Fischle W, Tseng BS, Dormann HL, et al：Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature　438：1116-1122, 2005

８) Schuettengruber B, Chourrout D, Vervoort M, et al：Genome regulation by polycomb and trithorax proteins. Cell　128：735-745, 2007

９) Stock JK, Giadrossi S, Casanova M, et al：Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat Cell Biol　9：1428-1435, 2007

10) Hampsey M, Reinberg D：Tails of intrigue：phosphorylation of RNA polymerase II mediates histone methylation. Cell　113：429-432, 2003

11) Pray-Grant MG, Daniel JA, Schieltz D, et al：Chd1 chromodomain links histone H3 methylation with SAGA-and SLIK-dependent acetylation. Nature　433：434-438, 2005

12) Dou Y, Milne TA, Tackett AJ, et al：Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell　121：873-885, 2005

13) Joshi AA, Struhl K：Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol Cell　20：971-978, 2005

14) Shi Y, Lan F, Matson C, et al：Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell　119：941-953, 2004

15) Metzger E, Wissmann M, Yin N, et al：LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature　437：436-439, 2005

16) Lan F, Bayliss PE, Rinn JL, et al：A histone H3 lysine 27 demethylase regulates animal posterior development. Nature　449：689-694, 2007

17) Agger K, Cloos PA, Christensen J, et al：UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature　449：731-734, 2007

18) Nakao M：Epigenetics：interaction of DNA methylation and chromatin. Gene　278：25-31, 2001

19) Sakamoto Y, Watanabe S, Ichimura T, et al：Overlapping roles of the methylated DNA-binding protein MBD1 and polycomb group proteins in transcriptional repression of HOXA genes and heterochromatin foci formation. J Biol Chem　282：16391-16400, 2007

20) Fujita N, Watanabe S, Ichimura T, et al：Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem　278：24132-24138, 2003

21) West AG, Gaszner M, Felsenfeld G：Insulators：many functions, many mechanisms. Genes Dev　16：271-288, 2002

22) Ishihara K, Oshimura M, Nakao M：CTCF-dependent chromatin insulator is linked to epigenetic remodeling. Mol Cell　23：733-742, 2006

23) Bell AC, Felsenfeld G：Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature　405：482-485, 2000

24) Hark AT, Schoenherr CJ, Katz DJ, et al：CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature　405：486-489, 2000

25) Misteli T：Protein dynamics：implications for nuclear architecture and gene expression. Science　291：843-847, 2001

26) Spector DL：The dynamics of chromosome organization and gene regulation. Annu Rev Biochem　72：573-608, 2003

27) Saitoh N, Spahr CS, Patterson SD, et al：Proteomic analysis of interchromatin granule clusters. Mol Biol Cell　15：3876-3890, 2004

28) Cioce M, Lamond AI：Cajal bodies：a long history of discovery. Annu Rev Cell Dev Biol　21：105-131, 2005

29) Schneider R, Grosschedl R：Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev　21：3027-3043, 2007

30) Cremer T, Cremer C：Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet　2：292-301, 2001

31) Kosak ST, Groudine M：Form follows function：The genomic organization of cellular differentiation. Genes Dev　18：1371-1384, 2004

32) Osborne CS, Chakalova L, Brown KE：Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet　36：1065-1071, 2004