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

染色体の構造と機能

著者： 久郷裕之¹ 押村光雄¹

所属機関： ¹鳥取大学大学院医学系研究科機能再生医科学専攻遺伝子機能工学部門

ページ範囲：P.605 - P.612

　染色体は細胞核内にあるDNA-蛋白質複合体であるが，その染色体は細胞が複製されたゲノム情報を分裂期に2つの娘細胞に正確に分配するために必須の構造体である．染色体の構造と機能を維持するためには，クロマチン構造に基づいた遺伝子発現制御を基盤としているエピジェネティクスが重要な役割を担っている．まさに，エピジェネティクスはクロマチンや染色体という複雑な高次構造体を制御するメカニズムそのものである．

参考文献

１) Jeppesen P：Histone acetylation：a possible mechanism for the inheritance of cell memory at mitosis. Bioessays　19：67-74, 1997

２) Martínez-López W, Folle GA, Obe G, et al：Chromosome regions enriched in hyperacetylated histone H4 are preferred sites for endonuclease-and radiation-induced breakpoints. Chromosome Res　9：69-75, 2001

３) Grigoryev SA, Bulynko YA, Popova EY：The end adjusts the means：heterochromatin remodelling during terminal cell differentiation. Chromosome Res 14：53-69, 2006

４) Schueler MG, Sullivan BA：Structural and functional dynamics of human centromeric chromatin. Annu Rev Genomics Hum Genet　7：301-313, 2006

５) Sullivan KF, Hechenberger M, Masri K：Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J Cell Biol　127：581-592, 1994

６) Zeitlin SG, Patel S, Kavli B, et al：Xenopus CENP-A assembly into chromatin requires base excision repair proteins. DNA Repair　4：760-772, 2005

７) Sullivan BA, Karpen GH：Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin an heterochromatin. Nat Struct Mol Biol　11：1076-1083, 2004

８) Jeppesen P, Mitchell A, Turner B, et al：Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes. Chromosoma　101：322-332, 1992

９) Hendzel MJ, Wei Y, Mancini MA, et al：Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma　106：348-360, 1997

10) Masumoto H, Nakano M, Ohzeki J：The role of CENP-B and alpha-satellite DNA：de novo assembly and epigenetic maintenance of human centromeres. Chromosome Res　12：543-556, 2004

11) Blower MD, Sullivan BA, Karpen GH：Conserved organization of centromeric chromatin in flies and humans. Dev Cell　2：319-330, 2002

12) Vos LJ, Famulski JK, Chan GK：How to build a centromere：from centromeric and pericentromeric chromatin to kinetochore assembly. Biochem Cell Biol　84：619-639, 2006

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

14) Lehnertz B, Ueda Y, Derijck AA, et al：Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol　13：1192-1200, 2003

15) Guenatri M, Bailly D, Maison C, et al：Mouse centric and pericentric satellite repeats form distinct functional heterochromatin. J Cell Biol　166：493-505, 2004

16) Fukagawa T, Nogami M, Yoshikawa M, et al：Dicer is essential for formation of the heterochromatin structure in vertebrate cells. Nat Cell Biol　6：784-791, 2004

17) de Lange T：Protection of mammalian telomeres. Oncogene 21：532-540, 2002

18) Blackburn EH：Switching and signaling at the telomere. Cell　106：661-673, 2001

19) Blasco MA：The epigenetics regulation of mammalian telomeres. Nat Rev Genet　8：299-309, 2007

20) Collins K, Mitchell JR：Telomerase in the human organism. Oncogene　21：564-579, 2002

21) Muntoni A, Reddel RR：The first molecular details of ALT in human tumor cells. Hum Mol Genet　14：R191-196, 2005

22) García-Cao M, O' Sullivan R, Peters AH, et al：Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet　36：94-99, 2004

23) Gonzalo S, García-Cao M, Fraga MF, et al：Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol　7：420-428, 2005

24) Gonzalo S, Jaco I, Fraga MF, et al：DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol　8：416-424, 2006

25) Steinert S, Shay JW, Wright WE：Modification of subtelomeric DNA. Mol Cell Biol　24：4571-4580, 2004

26) Okano M, Bell DW, Haber DA, et al：DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell　99：247-257, 1999

27) Benetti R, García-Cao M, Blasco MA：Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet　39：243-250, 2007