ゲノムネットワークプロジェクト

個別生命機能の解析
研究課題 脂肪・骨芽細胞分化ネットワークのクロストークと冗長性の解明
研究期間 平成16年度〜20年度
研究課題代表者 岡崎 康司
所属機関 埼玉医科大学 ゲノム医学研究センター
研究目的 脂肪細胞、骨芽細胞へ分化することが可能な間葉系幹細胞を用い、両者の分化に関わる転写制御系ネットワークを明らかにして双方のクロストークを見出し、脂質代謝および骨代謝を制御する創薬標的を発見することによって、骨粗鬆症やメタボリック症候群の治療に結び付けることを目的とする。
研究概要 脂肪細胞分化と骨芽細胞分化に関わる遺伝子発現変動について、ゲノム情報を駆使することによって網羅的に解析し、分化の方向性を決定し得る重要な遺伝子制御関係を明らかにしつつ、系統的な遺伝子ネットワークを描出する。特に、脂肪細胞分化の鍵因子であるPPARγの転写制御系ネットワークを描出することにより、PPARγ標的薬が影響を及ぼす範囲などを予測することが可能となり、副作用を軽減させた創薬の開発や効果の予測に貢献できると考えている。
研究成果 CAGE, PPI, ChIP-on-Chipなどのゲノムワイドな情報を活用して、PPARγを中心とする脂肪、骨芽細胞分化に関連する遺伝子を探索し、その制御関係を明らかにした。また、脂肪、骨芽細胞分化を制御する転写因子を新たに見いだし、そのクロストークにおける遺伝子制御関係を明らかにし、マウス個体においても検証した。
データ種別 ChIP-chip data(Agilent), Micro array data(Agilent)
対象生物 マウス、ヒト
組織・細胞株 ・ChIP-chip: embryo(3T3-L1)
・Microarray: adipose(DFAT-D1,DFAT-H)
・Microarray: bone marrow(ST2)
対象遺伝子 -
実験情報 ChiP-chip
アレイ名称:Agilent G4482A
抗体名:anti-PPARgamma

Microarray
アレイ名称:Affymetrix U133 Plus 2.0, Affymetrix GeneChip Mouse Genome 420 2.0 arrays
・pre-adipocyte
・adipogenesis(2days,4days,6days,8days,10days,time course)
産出データ
(ダウンロード)
・ヒトの脂肪細胞分化過程の発現プロファイル
・マウスの脂肪細胞分化過程の発現プロファイル
・PPARgammaに対する抗体で行ったChIPにて、脂肪細胞分化過程にあるマウス3T3L1細胞から得られた領域
・ゲノム上の転写因子結合部位予測データ
XMLデータ -
研究論文・特許出願・
学術発表など
------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:559
PUBLICATION TYPE: journal
PUBLICATION NAME: EMBO Journal
ARTICLE TITLE: Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in β-oxidation of fatty acids
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2006-11-01
TITLE: Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in β-oxidation of fatty acids
STATUS: Published
AUTHOR NAME: Igor V. Kurochkin1,2, Yumi Mizuno3, Akihiko Konagaya4, Yoshiyuki Sakaki5, Christian Schönbach1, 6 and Yasushi Okazaki3
AUTHOR AFFILIATION: 1 Immunoinformatics Team, Advanced Genome Information Group, RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan 2 Current address: Genome Annotation and Comparative Analysis Team, Computational and Experimental Systems Biology Group, RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan 3 Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Hidaka-shi, Saitama 350-1241, Japan 4 RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan 5 Computational and Experimental Systems Biology Group, RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan 6 Current address: Division of Genomics and Genetics, School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:713
PUBLICATION TYPE: Conference
PUBLICATION NAME: RCGMシンポジウム
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-07-27
TITLE: 比較ゲノム学的アプローチによる脂肪蓄積関連遺伝子の探索
STATUS: Presented
AUTHOR NAME: 八木 研 , 二階堂愛, 岡崎 康司
AUTHOR AFFILIATION: 埼玉医科大学ゲノム医学研究センター

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1015
PUBLICATION TYPE: journal
PUBLICATION NAME: FEBS Letters
ARTICLE TITLE: Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-09-14
TITLE: Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9.
STATUS: Published
AUTHOR NAME: Shigeki Arai, Akio Matsushita, Kun Du, Ken Yagi, Yasushi Okazaki and Riki Kurokawa
AUTHOR AFFILIATION: Research Center for Genomic Medicine, Saitama Medical University, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1155
PUBLICATION TYPE: journal
PUBLICATION NAME: FEBS letters
ARTICLE TITLE: Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-11-04
TITLE: Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9.
STATUS: Published
AUTHOR NAME: Shigeki Arai, Akio Matsushita, Kun Du, Ken Yagi, Yasushi Okazaki, Riki Kurokawa
AUTHOR AFFILIATION: Research center for genomic medicine, Saitama Medical University, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1173
PUBLICATION TYPE: Conference
PUBLICATION NAME: Poster in IMGC2007
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-10-30
TITLE: Analysis of micro RNAs involved in osteoblastic differentiation
STATUS: Presented
AUTHOR NAME: Yosuke Mizuno1, Ken Yagi1, Tatsuo Suda1, Takenobu Katagiri2, Toru Fukuda2, and Yasushi Okazaki1
AUTHOR AFFILIATION: 1Div. Funct. Genomics & Syst. Med. and 2Div. Pathophysiol., Res. Ctr. for Genomic Med., Saitama Med. Univ.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1236
PUBLICATION TYPE: Conference
PUBLICATION NAME: Bone Forum in Hanno
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-01-10
TITLE: 骨芽細胞分化に関与するマイクロRNAの探索
STATUS: Presented
AUTHOR NAME: 水野洋介
AUTHOR AFFILIATION: 埼玉医科大学ゲノム医学研究センターゲノム科学部門

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1237
PUBLICATION TYPE: journal
PUBLICATION NAME: BBRC
ARTICLE TITLE: MiR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-29
TITLE: MiR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation
STATUS: Published
AUTHOR NAME: Yosuke Mizuno(a), Ken Yagi(a), Yoshimi Tokuzawa(a), Yukiko Kanesaki-Yatsuka(a), Tatsuo Suda(a), Takenobu Katagiri(b), Toru Fukuda(b), Masayoshi Maruyama(c), Akihiko Okuda(c), Tomoyuki Amemiya(e), **, Yasumitsu Kondoh(e)**, Hideo Tashiro(e)*** and Yasushi Okazaki*(a,d)
AUTHOR AFFILIATION: (a)Division of Functional Genomics & Systems Medicine, (b)Division of Pathophysiology, (c)Division of Developmental Biology, (d)Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka city, Saitama 350-1241, Japan. (e)Probing Technology Laboratory, RIKEN, 2-1 Hirosawa, Wako city, Saitama, 351-0198, Japan. *Corresponding author ** Present address: Antibiotics Laboratory, RIKEN *** Present address: Nano Medical Engineering Laboratory

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1238
PUBLICATION TYPE: Conference
PUBLICATION NAME: BMB2007
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-11
TITLE: Analysis of micro RNAs involved in osteoblastic differentiation
STATUS: Presented
AUTHOR NAME: Yosuke Mizuno(1), Ken Yagi(1), Tatsuo Suda(1), Takenobu Katagiri(2), Toru Fukuda(2), and Yasushi Okazaki(1)
AUTHOR AFFILIATION: (1)Div. Funct. Genomics & Syst. Med. and (2)Div. Pathophysiol., Res. Ctr. for Genomic Med., Saitama Med. Univ.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1647
PUBLICATION TYPE: journal
PUBLICATION NAME: BBRC
ARTICLE TITLE: 4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor gamma agonist alleviates the symptoms of DSS-induced colitis.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-03-14
TITLE: 4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor gamma agonist alleviates the symptoms of DSS-induced colitis.
STATUS: Published
AUTHOR NAME: Keiko Yamamoto(a), (1), Yuichi Ninomiya(b), (1), Mioko Iseki(b), Yutaka Nakachi(c), Yukiko Kanesaki-Yatsuka(c), Yu Yamanoue(d), Toshimasa Itoh(d), Yasuho Nishii(c), Nikolai Petrovsky(e) and Yasushi Okazaki(b), (c)
AUTHOR AFFILIATION: (a)Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, (b)Division of Translational Research, Saitama Medical University, (c)Division of Functional Genomics & Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, (d)Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, (e)Diabetes and Endocrinology, Flinders Medical Centre, (1)These authors contributed equally to this work.

その他 『EMBO Journal』(2007 年2月7日号)に掲載
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