Chromatin dynamics and modulated cell-differentiation

• Project/Area Number: 17370084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: RIKEN
• Principal Investigator: YOKOYAMA Kazunari RIKEN, Gene Engineering Division, Senior researcher, 遺伝子材料研究室, 室長 (80182707)
• Co-Investigator(Kenkyū-buntansha): MURATA Takehide RIKEN, Gene Engineering Division, Senior researcher, 遺伝子材料研究室, 専任研究員 (50281621) ; KIMURA Makoto RIKEN, Gene Engineering Division, Senior researcher, 遺伝子材料研究室, 専任研究員 (00290891) ; PAN Jianzhi RIKEN, Gene Engineering Division, Researcher, 遺伝子材料研究室, 研究員 (80373356) ; OGURA Atsuo RIKEN, Bioresorce Engineering Division, Head, 遺伝子材料研究室, 室長 (20194524)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥14,700,000 (Direct Cost: ¥14,700,000); Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000); Fiscal Year 2005: ¥9,400,000 (Direct Cost: ¥9,400,000)
• Keywords: Chromatin / Histone caperon / Histone acetylation / Transcription factor / Remodeling / Histone deacetylation / Cell-differentiation / Adenovirusvector

Research Abstract

The structure of chromatin, which influences numerous DNA-associated phenomena, such as transcription, replication, recombination and repair, is controlled by a complex combination of histone modifications, ATP-dependent chromatin-remodeling enzymes, and nucleosome-assembly factors. The amino-terminal (N-terminal) tails of histones can be modified by acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation. We report here that transcription factor Jun dimerization protein 2 (JDP2) binds directly to histones and inhibits the p300-mediated acetylation both of core histones in vitro and of reconstituted nucleosomes that contain JDP2-recognition sequences. The 35 amino-terminal residues of JDP2 are required for histone-binding activity. The region encompassing both the histone-binding domain and the DNA-binding region is essential for the inhibition of histone acetylation by histone acetyltransferases (HAT). Moreover, assays of nucleosome assembly in vitro demonstrate that JDP2 also has histone-chaperone activity. Mutation of the region responsible for HAT-inhibition within JDP2 eliminates the repression of transcription from the c-jun promoter by JDP2, as well as the JDP2-mediated inhibition of RA-induced differentiation of F9 cells. Moreover, in an examination of Jdp2 "knock-out" (KO) mice, we observed elevated numbers of white adipocytes and the significant accumulation of lipid in the adipose tissue in sections of scapulae. In addition, mouse embryo fibroblasts (MEFs) from Jdp2 KO mice were more susceptible to adipocyte differentiation in response to hormonal induction and members of the C/EBP gene family were expressed at higher levels than was the case for MEFs from wild-type mice. Furthermore, JDP2 inhibited both the acetylation of histone H3 in the promoter of the gene for C/EBPδ and transcription from this promoter. Our data indicate that JDP2 plays a key role as a repressor of adipocyte differentiation by regulating the expression of the gene for C/EBPδ via inhibition of histone acetylation.

Research Products

• [Journal Article] E1A, E1B double-restricted adenovirus with RGD-Fiber modification exhibits enhanced oncolysis for CAR-deficient biliary cancers. (2007)
  • Author(s): Wakayama, M. et al.
  • Journal Title: Clinical Cancer Research. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nuclear Transfer of animal ES cells to study for the nuclear reprogramming of human stem cells. (2007)
  • Author(s): Saito, S. et al.
  • Journal Title: Methods in Molecular Biology (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] JDP2 suppresses adipocyte differentiation by regulating histone acetylation. (2007)
  • Author(s): Nakade, K. et al.
  • Journal Title: Cell Death and Differentiaton (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] E1A, E1B double-restricted adenovirus with RGD-Fiber modification exhibits enhanced oncolysis for CAR-deficient biliary cancers. (2007)
  • Author(s): Wakayama, M., Abei, M., Seo, E., Fukuda, K., Todoroki, T., Tanaka, N., Hamada, H., Yokoyama, K.
  • Journal Title: Clinical Cancer Research (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nuclear Transfer of animal ES cells to study for the nuclear reprogramming of human stem cells. (2007)
  • Author(s): Saito, S., Sawai, K., Murayama, Y., Fukuda K., Yokoyama, K.
  • Journal Title: Methods in Molecular Biology (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] JDP2 suppresses adipocyte differentiation by regulating histone acetylation. (2007)
  • Author(s): Nakade, K., Pan, J., Yoshiki, A., Ugai, H., Kimura, M., Liu, B., Li, H., Obata, Y., Iwama, M., Itohara, S., Murata, T., Yokoyama, K.
  • Journal Title: Cell Death and Differentiation (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation. (2006)
  • Author(s): Hayashi, R. et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 35633-35648
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cyclophilin a protects peg3 from hypermethylation and inactive histone modification. (2006)
  • Author(s): Lu, Y-C. et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 39081-39087
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C.et al.
  • Journal Title: Nature Structural ＆ Molecular Biology 13 Pages: 331-338
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene. (2006)
  • Author(s): Da, L.et al.
  • Journal Title: Biochem. J. 393 Pages: 779-788
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C, Kato, K, Chimura, T, Yamasaki, T, Nakade, K, Murata, T, Li, H, Pan, J, Zhao, M, Sun, K, Chiu, R, Ito, T, Nagata, K, Horikoshi, M, Yokoyama, K.
  • Journal Title: Nature Structural ＆ Molecular Biology 13 Pages: 331-338
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene. (2006)
  • Author(s): Da, L, Yokovama, K, Li, T, Zhao, M.
  • Journal Title: Biochem. J. 393 Pages: 779-788
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates E2F-dependent transcriptional activation and cell proliferation. (2006)
  • Author(s): Hayashi, R, Goto, Y, Ikeda, R, Yokoyama, K., Yoshida, K.
  • Journal Title: J. Biol. Chem. 281 Pages: 35633-35648
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cyclophilin a protects peg3 from hypermethylation and inactive histone modification. (2006)
  • Author(s): Lu, Y-C., Song, J., Cho, H-Y., Fan, G., Yokoyama.K., Chiu, R.
  • Journal Title: J. Biol. Chem. 281 Pages: 39081-39087
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JPD2. (2006)
  • Author(s): Jin, C.et al.
  • Journal Title: Nature Struc. Mo.1.Biol. 13 Pages: 331-338
• [Journal Article] Dual promoters control the cell-specific expression of the human cell death-induction DFF45-like effector B gene. (2006)
  • Author(s): Da, L.st al.
  • Journal Title: Biochem. J. 393 Pages: 779-788
• [Journal Article] CDCA4 Is an E2F transcription factoe family-induced nuclerar factor that regulates E2F-dependent transcriptional activation and cell proliferation. (2006)
  • Author(s): Hayashi, R. et al.
  • Journal Title: J.Biol.Chem. 281 Pages: 35633-35648
• [Journal Article] Cyclophilin a protects peg3 from hypermethylation and inactive histone modification. (2006)
  • Author(s): Lu, Y-C. st al.
  • Journal Title: J.Biol.Chem. 281 Pages: 39081-39087
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C.et al.
  • Journal Title: Nature Struc.Mol.Biol. (印刷中)
• [Journal Article] Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene. (2006)
  • Author(s): Da, L.et al.
  • Journal Title: Biochem.J. 393 Pages: 779-788
• [Journal Article] Gene silencing and histone modification by JDP2, a AP-1 repressor during the differentiation of embryonic stem cells. (2006)
  • Author(s): Liu, B.et al.
  • Journal Title: Current Topics in Genetics 1 Pages: 1-17
• [Journal Article] Derivation, maintenance, and induction of the differentiation in vitro of equine embryonic stem cells. Embryonic stem cell protocols. (2005)
  • Author(s): Saito, S. et al.
  • Journal Title: Methods in Molecular Biology 329 Pages: 57-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effective gene therapy for biliary tract cancer by a conditionally replicative adenovirus expressing uracil phosphoribosyltransferase. (2005)
  • Author(s): Seo, E.et al.
  • Journal Title: Cancer Research 65 Pages: 546-552
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recombinant Virus BANK for gene delivery. (2005)
  • Author(s): Yokoyama, K. et al.
  • Journal Title: Science 307 Pages: 1722-1722
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Purification of infectious adenovirus in two hours by ultracentrifugation and tangential flow filtration. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: Biochem. Biophys. Res. Commu. 331 Pages: 1053-1060
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: J. Gene Med. 7 Pages: 1148-1157
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5. (2005)
  • Author(s): Dietze, E.C. et al.
  • Journal Title: J. Cell Science 118 Pages: 5005-5022
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Adenovirus-mediated p53 gene transfer to the bile duct by direct administration into the bile in a rat cholangitis model. (2005)
  • Author(s): Kojima, Y. et al.
  • Journal Title: J. Surgical Res. 128 Pages: 126-131
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: Biochem. Biophys. Res. Commu. 337 Pages: 806-814
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Jun dimenigation protein 2 : A multifunctional transcription factor in mammalian cells. (2005)
  • Author(s): Yamasaki, T. et al.
  • Journal Title: Current Genomics 6 Pages: 351-364
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Derivation and induction of the differentiation of animal ES cells as well as human pluripotent stem cells derived from fetal membrane. (2005)
  • Author(s): Saito, S. et al.
  • Journal Title: Human Cell 18 Pages: 135-141
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Derivation, maintenance, and induction of the differentiation in vitro of equine embryonic stem cells. Embryonic stem cell protocols; vol. 1 (ed. by K. Turksen) (Humana Press Inc., Totowa, NJ) (2005)
  • Author(s): Saito, S, Sawai, K, Minamihashi, A, Ugai, H, Murata. T., Yokoyama, K.
  • Journal Title: Methods in Molecular Biology 329 Pages: 59-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effective gene therapy for biliary tract cancer by a conditionally replicative adenovirus expressing uracil phosphoribosyltransferase : Significance of timing of 5-floourouracil administration (2005)
  • Author(s): Seo, E, Abei, M, Wakayama, M, Fukuda, K, Ugai, H, Murata, T, Todoroki, T, Tanaka, N, Hamada, H, Yokoyama, K.
  • Journal Title: Cancer Research 65 Pages: 546-552
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Recombinant Virus BANK for gene delivery. (2005)
  • Author(s): Yokoyama, K, Murata, T, Ugai, H, Suzuki, E, Terashima, M, Kujime, Y, Inamoto, S, Hirose, M, Inabe, K, Yamasaki, T.
  • Journal Title: Science 307 Pages: 1722-1722
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Purification of infectious adenovirus in two hours by ultracentrifugation and tangential flow filtration. (2005)
  • Author(s): Ugai, H, Yamasaki, T, Hirose, M, Inabe, K, Kujime, Y, Terashima, M, Liu, B, Tang, H, Zhao, M, Murata, T, Kimura, M, Pan, J, Obata, Y, Hamada, H, Yokoyama, K.
  • Journal Title: Biochem. Biophys. Res. Commu. 331 Pages: 1053-1060
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank. (2005)
  • Author(s): Ugai, H, Murata, T, Nagamura, Y, Ugawa, Y, Suzuki, E, Nakata, H, Kujime, Y, Inamoto, S, Hirose, M, Inabe, K, Terashima, M, Yamasaki, T, Liu, B, Nakade, K, Pan, J, Kimura, M, Saito, I, Hamada, H, Obata, Y, Yokoyama, K.
  • Journal Title: J. Gene Med. 7 Pages: 1148-1157
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5. (2005)
  • Author(s): Dietze, E.C, Bowie, M.L, Mrozek, K, Caldwell, E, Neal, C, Marjoram, R.J, Troch, M.M, Bean, G.R, Yokoyama, K, Ibarra, C.A, Seewaldt, V.L.
  • Journal Title: J. Cell Science 118 Pages: 5005-5022
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adenovirus-mediated p53 gene transfer to the bile duct by direct administration into the bile in a rat cholangitis model. (2005)
  • Author(s): Kojima, Y, Honda, K, Kotegawa, H, Kushihata, F, Kobayashi, N, Yokovama, K, Hamada, H.
  • Journal Title: J. Surgical Res. 128 Pages: 126-131
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses. (2005)
  • Author(s): Ugai, H, Inabe, K., Yamasaki, T, Murata, T, Obata, Y., Hamada, H, Yokovama, K.
  • Journal Title: Biochem. Biophys. Res. Commu. 337 Pages: 806-814
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Jun dimenigation protein 2 : A multifunctional transcription factor in mammalian cells. (2005)
  • Author(s): Yamasaki, T, Noguchi, M, Liu, B, Nakade, K, Wang, P-C., Murata, T, Yokoyama, K.
  • Journal Title: Current Genomics 6 Pages: 351-364
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Derivation and induction of the differentiation of animal ES cells as well as human pluripotent stem cells derived from fetal membrane. (2005)
  • Author(s): Saito, S, Yokoyama, K, Tamagawa, T, Ishiwata, I.
  • Journal Title: Human Cell 18 Pages: 135-141
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effective gene therapy for biliary tract cancer by a conditionally replicative adenovirus expressing uracil phosphoribosyltransferase : Significance of timing of 5-fluorouracil administration. (2005)
  • Author(s): Seo, E.et al.
  • Journal Title: Cancer Research 65 Pages: 546-552
• [Journal Article] CREB-binding protein regulates apoptosis and growth of HMECs grown in reconstituted ECM via laminin-5. (2005)
  • Author(s): Dietze, E.C. et al.
  • Journal Title: J.Cell Science 118 Pages: 5005-5022
• [Journal Article] A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: J.Gene Med. 7 Pages: 1148-1157
• [Journal Article] Adenovirus-mediated p53 gene transfer to the bile duct by direct administration into the bile in a rat cholangitis model. (2005)
  • Author(s): Kojima, Y. et al.
  • Journal Title: J.Surgical Res. 128 Pages: 126-131
• [Journal Article] Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: Biochem.Biophys.Res.Commu. 337 Pages: 806-814
• [Journal Article] Derivation and induction of the differentiation of animal ES Cells as well as human pluripotent stem Cells derived from fetal membrane. (2005)
  • Author(s): Sito, S. et al.
  • Journal Title: Human Cell 18 Pages: 135-141
• [Journal Article] Derivation, maintenance, and induction of the differentiation in vitro of equine embryonic stem cells. (2005)
  • Author(s): Saito, S. et al.
  • Journal Title: Methods in Molecular Biology 329 Pages: 59-79
• [Journal Article] Purification of infectious adenovirus in two hours by ultracentrifugation and tangential flow filtration. (2005)
  • Author(s): Ugai, H. et al.
  • Journal Title: Biochem.Biophys.Res.Commu. 331 Pages: 1053-1060
• [Journal Article] EIA,EIB double-restricted adenovirus with RGD-Fiber modification exhibits enhanced oncolysis for CAR-deficient biliary cancers.
  • Author(s): Wakayama, M. st al.
  • Journal Title: Clin.Cancer.Res. (in press)
• [Journal Article] Nuclear Transfer of animal ES cells to study for unclear reprogramming of human stem cells.Neural stem cells
  • Author(s): Saito, S. et al.
  • Journal Title: Methods in Mo1.Biol. (in press)
• [Journal Article] Function of sequence-specific histone chaperon JDP2.
  • Author(s): Yokoyama, K st al.
  • Journal Title: current Topics in Biology Research (in press)