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KLF14 biology: its physiological roles and transcriptional regulation

Research Project

Project/Area Number 25460409
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human genetics
Research InstitutionNational Center for Child Health and Development

Principal Investigator

NAKABAYASHI Kazuhiko  国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557)

Co-Investigator(Renkei-kenkyūsha) TAKADA Shuji  国立成育医療研究センター, 研究所, 部長 (20382856)
TOMIKAWA Junko  国立成育医療研究センター, 研究所, 研究員 (80534990)
TAYAMA Chiharu  国立成育医療研究センター, 研究所, 研究員 (60774445)
Research Collaborator SUGAHARA Naoko  国立成育医療研究センター, 研究所, 研究補助員
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsゲノムインプリンティング / KLF14 / 白色脂肪組織 / Klf14 / genomic imprinting / white adipose tissue
Outline of Final Research Achievements

KLF14 has been proposed to act as a master regulator of key metabolic genes in adipose tissue. Cis-regulatory SNPs in the KLF14 locus are associated with susceptibility to multiple metabolic diseases including T2D. We aimed to elucidate physiological functions of KLF14 in the white adipose tissue (WAT), and to establish materials and methods to study molecular mechanisms underlying imprinted gene expression of Mest and Klf14 genes, which are located within a 200kb genomic interval.
We revealed that KLF14 involves in controlling obesity-induced inflammation in WAT by analyzing the phenotype of Klf14 knockout mice. We also successfully established mouse lines with a targeted deletion of the germline differentially methylated region at the Mest promoter region, which is expected to play a central role in the regulation of imprinted expression of Klf14.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014 2013

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 17 results,  Open Access: 14 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.2017

    • Author(s)
      Kagami M, Matsubara K, Nakabayashi K, Nakamura A, Sano S, Okamura K, Hata K, Fukami M, Ogata T.
    • Journal Title

      Genet Med.

      Volume: 19 Issue: 4 Pages: 476-482

    • DOI

      10.1038/gim.2016.123

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions.2016

    • Author(s)
      Morita S, Noguchi H, Horii T, Nakabayashi K, Kimura M, Okamura K, Sakai A, Nakashima H, Hata K, Nakashima K, Hatada I
    • Journal Title

      Nat Biotechnol.

      Volume: 34 Issue: 10 Pages: 1060-1065

    • DOI

      10.1038/nbt.3658

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.2016

    • Author(s)
      Sanchez-Delgado M, Court F, Vidal E, Medrano J, Monteagudo-Sanchez A, Martin-Trujillo A, Tayama C, Iglesias-Platas I, Kondova I, Bontrop R, Poo-Llanillo ME, Marques-Bonet T, Nakabayashi K, Simon C, Monk D.
    • Journal Title

      PLoS Genet.

      Volume: 12 Issue: 11 Pages: e1006427-e1006427

    • DOI

      10.1371/journal.pgen.1006427

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changeability of the fully methylated status of the 15q11.2 region in induced pluripotent stem cells derived from a patient with Prader-Willi syndrome.2016

    • Author(s)
      Okuno H, Nakabayashi K, Abe K, Ando T, Sanosaka T, Kohyama J, Akamatsu W, Ohyama M, Takahashi T, Kosaki K, Okano H.
    • Journal Title

      Congenit Anom (Kyoto)

      Volume: Dec 21 Issue: 4 Pages: 96-103

    • DOI

      10.1111/cga.12206

    • NAID

      130008142312

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive.2016

    • Author(s)
      Maupetit-Méhouas S, Montibus B, Nury D, Tayama C, Wassef M, Kota SK, Fogli A, Cerqueira Campos F, Hata K, Feil R, Magueron R, Nakabayashi K, Court F, Arnaud P
    • Journal Title

      Nucleic Acids Res.

      Volume: 44 Issue: 2 Pages: 621-635

    • DOI

      10.1093/nar/gkv960

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genomic, epigenomic, and transcriptomic profiling towards identifying omics -features and specific biomarkers that distinguish uterine leiomyosarcoma and leiomyoma at molecular levels.2015

    • Author(s)
      Miyata T, Sonoda K, Tomikawa J, Tayama C, Maehara K, Kobayashi H, Wake N, Kato K, Hata K, Nakabayashi K
    • Journal Title

      Sarcoma

      Volume: 2015 Pages: 412068-412068

    • DOI

      10.1155/2015/412068

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity.2015

    • Author(s)
      Morita S, Nakabayashi K, Kawai T, Hayashi K, Horii T, Kimura M, Kamei Y, Ogawa Y, Hata K, Hatada I
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 21693-21693

    • DOI

      10.1038/srep21693

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lists of HumanMethylation450 BeadChip probes with nucleotide-variant information obtained from the Phase 3 data of the 1000 Genomes Project.2015

    • Author(s)
      Okamura K, Kawai T, Hata K, Nakabayashi K
    • Journal Title

      Genomics Data

      Volume: 7 Pages: 67-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Absence of maternal methylation in biparental hydatidiform moles with NLRP7 maternal-effect mutations reveals widespread placenta-specific imprinting.2015

    • Author(s)
      Sanchez-Delgado M, Martin-Trujillo A, Tayama C, Vidal E, Esteller M, Iglesias-Platas I, Deo N, Barney O, Maclean K, Hata K, Nakabayashi K, Fisher R, Monk D
    • Journal Title

      PLoS Genet.

      Volume: 11

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An insulator element located at the cyclin B1 interacting protein 1 gene locus is highly conserved among mammalian species.2015

    • Author(s)
      Yoshida W, Tomikawa J, Inaki M, Kimura H, Onodera M, Hata K, Nakabayashi K
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: e0131204-e0131204

    • DOI

      10.1371/journal.pone.0131204

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation2015

    • Author(s)
      Miyata K, Miyata T, Nakabayashi K, Okamura K, Naito M, Kawai T, Takada S, Kato K, Miyamoto S, Hata K, Asahara H
    • Journal Title

      Hum. Mol. Genet.

      Volume: 24 Issue: 2 Pages: 410-423

    • DOI

      10.1093/hmg/ddu457

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of maternal-specific H3K9me3 modification in establishing imprinted X-chromosome inactivation and embryogenesis in mice.2014

    • Author(s)
      Fukuda A, Tomikawa J, Miura T, Hata K, Nakabayashi K, Eggan K, Akutsu H, Umezawa A.
    • Journal Title

      Nat Commun.

      Volume: 5 Issue: 1 Pages: 5464-5464

    • DOI

      10.1038/ncomms6464

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Offspring production with sperm grown in vitro from cryopreserved testis tissues2014

    • Author(s)
      Yokonishi T, Sato T, Komeya M, Katagiri K, Kubota Y, Nakabayashi K, Hata K, Inoue K, Ogonuki N, Ogura A, Ogawa T
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 4320-4320

    • DOI

      10.1038/ncomms5320

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions (DMRs) to aberrant methylation in Beckwith-Wiedemann syndrome with epimutations2014

    • Author(s)
      Maeda T, Higashimoto K, Jozaki K, Hitomi H, Nakabayashi K, Makita Y, Tonoki H, Okamoto N, Takada F, Ohashi H, Migita M, Kosaki R, Matsubara K, Ogata T, Matsuo M, Hamasaki Y, Ohtsuka Y, Nishioka K, Joh K, Mukai T, Hata K, Soejima H
    • Journal Title

      Genet Med

      Volume: 16(12) Issue: 12 Pages: 903-912

    • DOI

      10.1038/gim.2014.46

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer.2014

    • Author(s)
      Romanelli V, Nakabayashi K, Vizoso M, Moran S, Iglesias-Platas I, Sugahara N, Simón C, Hata K, Esteller M, Court F, Monk D.
    • Journal Title

      Epigenetics

      Volume: 9 Issue: 5 Pages: 783-790

    • DOI

      10.4161/epi.28323

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of the human imprintome and suggests a germline methylation independent establishment of imprinting.2014

    • Author(s)
      Court F, Tayama C, Romanelli V, Martin-Trujillo A, Iglesias-Platas I, Okamura K, Sugahara N, Simon C, Moore H, Harness J, Keirstead H, Vicente Sanchez-Mut J, Kaneki E, Lapunzina P, Soejima H, Wake N, Esteller M, Ogata T, Hata K, Nakabayashi K, Monk D*
    • Journal Title

      Genome Res

      Volume: in press Issue: 4 Pages: 554-569

    • DOI

      10.1101/gr.164913.113

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic and transcriptional features of the novel human imprinted lncRNA GPR1AS suggest it is a functional ortholog to mouse Zdbf2linc.2013

    • Author(s)
      Kobayashi H, Yanagisawa E, Sakashita A, Sugawara N, Kumakura S, Ogawa H, Akutsu H, Hata K, Nakabayashi K, Kono T.
    • Journal Title

      Epigenetics

      Volume: 8 (6) Issue: 6 Pages: 635-645

    • DOI

      10.4161/epi.24887

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] KLF14 involves in controlling inflammation in the white adipose tissue.2016

    • Author(s)
      Tayama C, Takanashi R, Tomikawa J, Okita H, Hata K, Okamura T, Nakabayashi K.
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 父性遺伝する食事誘導性肥満におけるインプリント遺伝子の解析と新規インプリント遺伝子の探索について.2016

    • Author(s)
      森田純代,中林一彦,河合智子,林恵子,堀居拓郎,木村美香,亀井康富,小川佳宏,秦健一郎,畑田出穂
    • Organizer
      第10回日本エピジェネティクス研究会年会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
  • [Presentation] 成育・周産期関連疾患解明のためのエピゲノム解析2016

    • Author(s)
      中林一彦
    • Organizer
      金沢大学学際科学実験センター・サイエンスセミナー
    • Place of Presentation
      金沢
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 転写因子 KLF14 の白色脂肪組織における炎症制御への関与2015

    • Author(s)
      中林一彦,田山千春,高梨理絵子,冨川順子,大喜多肇,秦健一郎,岡村匡史
    • Organizer
      日本人類遺伝学会第60回大会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] KLF14 involves in controlling inflammation in the white adipose tissue.2015

    • Author(s)
      Tayama C, Takanashi E, Tomikawa J, Okita H, Hata K, Okamura T, Nakabayashi K
    • Organizer
      The 65th Annual Meeting of the American Society of Human Genetics
    • Place of Presentation
      Baltimore
    • Year and Date
      2015-10-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 次世代シーケンサーを用いた遺伝子・ゲノム診断2015

    • Author(s)
      中林一彦
    • Organizer
      第25回日本サイトメトリー学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-12
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 転写因子KLF14の白色脂肪組織における炎症制御への関与2014

    • Author(s)
      田山 千春,高梨(矢延) 理絵子,富川 順子,大喜多 肇,秦 健一郎,岡村 匡史,中林 一彦
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒトインプリントーム解析から見えてきたヒト(霊長類)特異的エピゲノム進化2014

    • Author(s)
      中林一彦
    • Organizer
      京都大学霊長類研究所・研究会「霊長類への展開に向けた幹細胞・生殖細胞・エピゲノム研究」
    • Place of Presentation
      京都大学・霊長類研究所
    • Year and Date
      2014-08-27
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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