エピゲノム技術開発ユニット

細胞内の全DNAの塩基配列情報をさす「ゲノム」に対し、DNAの化学修飾や構造変化などで細胞の個性を記憶する情報を「エピゲノム」とよびます。エピゲノムはがん化など細胞の異常にも関わっている可能性があり、個々の疾患に関わるエピゲノムを解析することが診断や創薬に重要です。当ユニットは次世代のゲノミクスデータ解析に有用な新規の技術シーズ、特に、単一細胞に適用できるエピゲノム解析法を開発します。

研究分野

生物学 & 生化学 / 分子生物 & 遺伝学

研究テーマ

• 単一細胞エピゲノム解析法の開発
• がん幹細胞や老化細胞を含む疾患細胞に対する単一細胞エピゲノム解析
• 単一細胞のエピゲノム情報に基づいた治療標的分子の同定

主要論文

1. *Kharchenko, PV., Alekseyenko, AA., Schwartz, YB., Minoda, A., Riddle, NC., Ernst, J., Sabo, PJ., Larschan, E., Gorchakov, AA., Gu, T., Linder-Basso, D., Plachetka, A., Shanower, G., Tolstorukov, MY., Luquette, LJ., Xi, R., Jung, YL., Park, RW., Bishop, EP., Canfield, TK., Sandstrom, R., Thurman, RE., MacAlpine, DM., Stamatoyannopoulos, JA., Kellis, M., Elgin, SC., Kuroda, MI., Pirrotta, V., Karpen, GH., Park, PJ.
   "Comprehensive analysis of the chromatin landscape in Drosophila melanogaster"
   Nature 471, 480-5 (2011)
2. *Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB, Tolstorukov MY, Gorchakov AA, Jaffe JD, Kennedy C, Linder-Basso D, Peach SE, Shanower G, Zheng H, Kuroda MI, Pirrotta V, Park PJ, Elgin SC, Karpen GH.
   "Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin"
   Genome Res. 21(2), 147-63　(2011)
3. *Egelhofer TA, Minoda A, Klugman S, Lee K, Kolasinska-Zwierz P, Alekseyenko AA, Cheung MS, Day DS, Gadel S, Gorchakov AA, Gu T, Kharchenko PV, Kuan S, Latorre I, Linder-Basso D, Luu Y, Ngo Q, Perry M, Rechtsteiner A, Riddle NC, Schwartz YB, Shanower GA, Vielle A, Ahringer J, Elgin SC, Kuroda MI, Pirrotta V, Ren B, Strome S, Park PJ, Karpen GH, Hawkins RD, Lieb JD.
   "An assessment of histone-modification antibody quality"
   Nat Struct Mol Biol. 18(1), 91-3 (2011)
4. *modENCODE Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, Eaton ML, Landolin JM, Bristow CA, Ma L, Lin MF, Washietl S, Arshinoff BI, Ay F, Meyer PE, Robine N, Washington NL, Di Stefano L, Berezikov E, Brown CD, Candeias R, Carlson JW, Carr A, Jungreis I, Marbach D, Sealfon R, Tolstorukov MY, Will S, Alekseyenko AA, Artieri C, Booth BW, Brooks AN, Dai Q, Davis CA, Duff MO, Feng X, Gorchakov AA, Gu T, Henikoff JG, Kapranov P, Li R, MacAlpine HK, Malone J, Minoda A, Nordman J, Okamura K, Perry M, Powell SK, Riddle NC, Sakai A, Samsonova A, Sandler JE, Schwartz YB, Sher N, Spokony R, Sturgill D, van Baren M, Wan KH, Yang L, Yu C, Feingold E, Good P, Guyer M, Lowdon R, Ahmad K, Andrews J, Berger B, Brenner SE, Brent MR, Cherbas L, Elgin SC, Gingeras TR, Grossman R, Hoskins RA, Kaufman TC, Kent W, Kuroda MI, Orr-Weaver T, Perrimon N, Pirrotta V, Posakony JW, Ren B, Russell S, Cherbas P, Graveley BR, Lewis S, Micklem G, Oliver B, Park PJ, Celniker SE, Henikoff S, Karpen GH, Lai EC, MacAlpine DM, Stein LD, White KP, Kellis M.
   "Identification of functional elements and regulatory circuits by Drosophila modENCODE"
   Science 330(6012), 1787-97 (2010)
5. *Chiolo I, Minoda A, Colmenares SU, Polyzos A, Costes SV, Karpen GH.
   "Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair"
   Cell 144(5), 732-44, (2011)
6. *Riddle NC, Jung YL, Gu T, Alekseyenko AA, Asker D, Gui H, Kharchenko PV, Minoda A, Plachetka A, Schwartz YB, Tolstorukov MY, Kuroda MI, Pirrotta V, Karpen GH, Park PJ, Elgin SC.
   "Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain"
   PLoS Genet. 8(9):e1002954 (2012)
7. *Schwartz YB, Linder-Basso D, Kharchenko PV, Tolstorukov MY, Kim M, Li HB, Gorchakov AA,Minoda A, Shanower G, Alekseyenko AA, Riddle NC, Jung YL, Gu T, Plachetka A, Elgin SC, Kuroda MI, Park PJ, Savitsky M, Karpen GH, Pirrotta V.
   "Nature and function of insulator protein binding sites in the Drosophila genome"
   Genome Res. 22(11), 2188-98 (2012)
8. *Alekseyenko AA, Ho JW, Peng S, Gelbart M, Tolstorukov MY, Plachetka A, Kharchenko PV, Jung YL, Gorchakov AA, Larschan E, Gu T, Minoda A, Riddle NC, Schwartz YB, Elgin SC, Karpen GH, Pirrotta V, Kuroda MI, Park PJ.
   "Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context"
   PLoS Genet. 8(4), e1002646 (2012)
9. *Minoda A, Saitoh S, Takahashi K, Toda T.
   "BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere"
   Mol Biol Cell. 16(1), 316-27 (2005)