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Epigenetic regulation of aromatase gene by changes of chromatin structure

Research Project

Project/Area Number 22591019
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionFujita Health University

Principal Investigator

HARADA Nobuhiro  藤田保健衛生大学, 医学部, 教授 (00189705)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Satoru  藤田保健衛生大学, 医学部, 講師 (00300723)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords内分泌学 / エストロゲン / アロマターゼ / クロマチン / エピジェネティック / アセチル化 / メチル化 / ヒストン / 組織特異的発現 / クロマチン構造 / ポリコーム / ヒストンH3 / ポリコーム群タンパク質
Research Abstract

The human aromatase (CYP19) gene has three major promoters. Human placenta-derived JEG3, hepatoma-derived HepG2, and ovary-derived KGN cells mainly utilize the promoters Ia, Ib, and Ic, respectively. In order to evaluate histone modifications responsible for these promoter usages, we first performed ChIP assays, which are well-known as epigenetic markers of transcribed loci. The results showed that lysine 27 of histone H3 at the inactive promoters was apparently trimethylated and the trimethylated levels at the resting promoters was higher than that at the active one. These suggest that alternative promoter usage in the CYP19 locus is controlled by this silencing complex recruited by tri-methylation of lysine 27 of histone H3.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (33 results)

All 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (18 results) (of which Invited: 1 results) Book (1 results) Remarks (3 results)

  • [Journal Article] LIM-homeo domain transcription factor, Lhx2, is involved in transcriptional control of brain-specific promoter/exon 1f of the2012

    • Author(s)
      Honda, S.-I., Kozako, T., Shimeno, H.
    • Journal Title

      J Neuro

      Volume: 66(2) Issue: 11 Pages: 260-272

    • DOI

      10.1111/j.1365-2826.2012.02356.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] LIM-homeodomain transcription factor, Lhx2, is involved in transcriptional control of brain-specific promoter/exon 1f of the mouse aromatase gene2012

    • Author(s)
      Honda, S.-I.
    • Journal Title

      J. Neuroendocrinol.

      Volume: 24 Pages: 1367-1374

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral analysis of genetically modified mice indicates essential roles2011

    • Author(s)
      Honda S-I, Wakatsuki T, Harada
    • Journal Title

      Front

      Volume: 2 Pages: 40-40

    • DOI

      10.3389/fendo.2011.00040

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human and quail arom-atase activity is rapidly and reversibly inhibited by phosphorylating condi2011

    • Author(s)
      Charlier TD, Harada N, Balthazart J
    • Journal Title

      Endocrinology

      Volume: 152(11) Issue: 11 Pages: 4199-4210

    • DOI

      10.1210/en.2011-0119

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathological role of androstene-3β, 17β-diol2011

    • Author(s)
      Honma, N.
    • Journal Title

      Cancer Sci.

      Volume: 102 Pages: 1848-1854

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estradiol promotes Purkinje dendritic growth, spinogenesis and synaptogenesis during neonatal life by inducing the expression of BDNF2011

    • Author(s)
      Shogo Haraguchi
    • Journal Title

      The Cerebellum

      Volume: (in press) Issue: 2 Pages: 416-417

    • DOI

      10.1007/s12311-011-0342-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The androgen receptor governs execution butnot2010

    • Author(s)
      Juntti SA, Tollkuhn J, Wu MV, Fraser EJ, Soderborg T, Tan S, Honda S-I
    • Journal Title

      Neuron

      Volume: 66(2) Issue: 2 Pages: 260-272

    • DOI

      10.1016/j.neuron.2010.03.024

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates β-secretase (BACW1) and prevents Alzheimer-like pathology and cognitive impairment.2010

    • Author(s)
      McAllister G, Long J, Bowers A, Walker A, Cao P, Honda S-I, Harada N, Staufenbiel M, Shen Y, Li R.
    • Journal Title

      J Neurosci

      Volume: 30 (21) Issue: 21 Pages: 7326-7334

    • DOI

      10.1523/jneurosci.1180-10.2010

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor 1 enhances the aromatase P450 expression by inhibiting auto- phagy2010

    • Author(s)
      Zhang B, Shozu M, Okada M, Ishikawa H, Kasai T, Murakami K, Nomura K, Harada N, Inoue M
    • Journal Title

      Endocrinology

      Volume: 151(10) Issue: 10 Pages: 4949-4958

    • DOI

      10.1210/en.2010-0294

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates β-secretase (BACW1) and prevents Alzheimer-like pathology and cognitive impairment2010

    • Author(s)
      McAlister, G.
    • Journal Title

      J.Neurosci.

      Volume: 30(21) Pages: 7326-7334

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor 1 enhances the aromatase P450 expression by inhibiting autophagy2010

    • Author(s)
      Zhang, B.
    • Journal Title

      Endocrinology

      Volume: 151(10) Pages: 4949-4958

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Transcriptional and post-translational regulation of aromatase in the mouse brain.2012

    • Author(s)
      Harada N & Honda S-I.
    • Organizer
      15th International Congress on Hormonal Steroids and Hormones & Cancer;
    • Place of Presentation
      Kanazawa, Japan.
    • Related Report
      2012 Final Research Report
  • [Presentation] The stability of P450arom is controlled by Ca2+ -dependent phosphorylation and dephosphorylation.2012

    • Author(s)
      Hayashi T, Munetsuna E, & Harada N.
    • Organizer
      15th Inter- national Congress on Hormonal Steroids and Hormones & Cancer;
    • Place of Presentation
      Kanazawa, Japan.
    • Related Report
      2012 Final Research Report
  • [Presentation] A dense chromatin structure select- ively represses a promoter(s) of the CYP19 gene producing several trans- cripts by alternative promoter usage.2012

    • Author(s)
      Kotomura N, Harada N, Ishihara S.
    • Organizer
      第6回日本エピジェネティック研究会年会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] Ca2+依存的リン酸化はエストロゲン合成酵素アロマターゼの活性・安定性を調節する.2012

    • Author(s)
      林孝典、宗綱栄二、原田信広
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] アロマターゼの脳特異的発現に関与する転写因子Deaf-1の機能ドメインの解析2012

    • Author(s)
      本田伸一郎、大下遥子、民本愛、小迫知弘、蔵元佑嘉子、元流梨恵、原田信広、添田秦司.
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] プロモーターの転写活性を決めるクロマチン構造2012

    • Author(s)
      琴村直恵、原田信広、石原悟
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] Transcriptional and Post-Transcriptional Regulation of Aromatase in the Mouse Brain2012

    • Author(s)
      Nobuhiro Harada
    • Organizer
      15th International Congress on Hormonal Steroids and Hormones & cancer
    • Place of Presentation
      Kanazawa
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ヒストンH3K27のトリメチル化によるアロマターゼ遺伝子プロモーターの選択的不活性化2011

    • Author(s)
      石原悟
    • Organizer
      第19回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      福岡大学病院メディカルホール
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Condensed Chromatin Marked by K27-trimethylated Histone H3 Determines Alternative Promoter Usage of the Cyp19 Gene2011

    • Author(s)
      Naoe Kotomura
    • Organizer
      CDB Symposium 2011
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2011-03-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Function and regulation of aromatase/estrogen in the brain.2011 International Mini-Conference on Translational Neuroscience: Neuro- logical2011

    • Author(s)
      Harada N
    • Organizer
      Disorders and Psychiatric Diseases (IMCOTN-NDPD)
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Final Research Report
  • [Presentation] Condensed chromatin marked by K27-trimethylated histone H3 deter- mines alternative promoter usage of the CYP19 gene.2011

    • Author(s)
      Kotomura N, Harada N, Ishihara S
    • Organizer
      CDB Symposium2011: Epigenetic Landscape in Devel- opment and Diseases
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Ca2+依存性リン酸化・脱リン酸化によるエストロゲン合成酵素P450aromの分解制御される.2011

    • Author(s)
      林孝典、原田信広
    • Organizer
      第19回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒストンH3K27トリメチル化によるアロマターゼ遺伝子プロモーターの選択的不活性化2011

    • Author(s)
      石原悟、琴村直恵、西芳寛、野村政壽、柳瀬敏彦、原田信広
    • Organizer
      第19回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] The contribution of histone modifi- cations to alternative promoter usage of the human CYP19 gene.2011

    • Author(s)
      Kotomura N, Harada N, Ishihara S.
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] エストロゲン合成酵素P450aromの安定性はCa2+依存性リン酸化・脱リン酸化による制御される.2011

    • Author(s)
      林孝典、原田信広
    • Organizer
      第84回日本生化学会大会合同大会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] Condensed chromatin marked by K27-trimethylated histone H3 deter- mines alternative promoter usage of the CYP19 gene.2011

    • Author(s)
      Kotomura N, Harada N, Ishihara S
    • Organizer
      第5回日本エピジェネティ ック研究会年会
    • Place of Presentation
      熊本
    • Related Report
      2012 Final Research Report
  • [Presentation] アロマターゼ遺伝子CYP19のプロモーター選択に関するエピジェネティックス解析2010

    • Author(s)
      石原悟、琴村直恵、原田信広
    • Organizer
      第18回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Final Research Report
  • [Presentation] エストロゲン合成酵素アロマターゼの安定性はリン酸化によって制御される2010

    • Author(s)
      林孝典、若月徹、吉村憲子、原田信広
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Book] Brain Aromatase, Estrogens, and Behavior2012

    • Author(s)
      Nobuhiro Harada & Shin-ichiro Honda
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/~biochem/

    • Related Report
      2012 Final Research Report
  • [Remarks] 研究業績

    • URL

      http://www.fujita-hu.ac.jp/~biochem/2008/paper.html

    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究内容

    • URL

      http://www.fujita-hu.ac.jp/~biochem/2008/research.html

    • Related Report
      2012 Annual Research Report

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Published: 2010-11-30   Modified: 2019-07-29  

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