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Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus

Research Project

Project/Area Number 15H02373
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical genome science
Research InstitutionNational Institute of Genetics

Principal Investigator

Inoue Ituro  国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500)

Co-Investigator(Kenkyū-buntansha) 佐藤 健人  東海大学, 医学部, 准教授 (50235363)
細道 一善  金沢大学, 医学系, 准教授 (50420948)
Co-Investigator(Renkei-kenkyūsha) ENOMOTO Takayuki  新潟大学, 医歯学系, 教授 (90283754)
AKIRA Shigeo  日本医科大学, 医学部, 教授 (40231849)
Research Collaborator NAKAOKA Hirofumi  国立遺伝学研究所, 総合遺伝研究系, 助教 (70611193)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2016: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2015: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Keywords子宮内膜症 / アレル優位性 / エンハンサー活性 / クロマチン高次構造 / 疾患関連遺伝子 / 遺伝学
Outline of Final Research Achievements

We explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging“allele-specific”functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. The protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by chromatin immunoprecipitation (ChIP) analyses. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (29 results)

All 2018 2017 2016 2015

All Journal Article (23 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 22 results,  Open Access: 20 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer2018

    • Author(s)
      Ishimine M, Lee HC, Nakaoka H, Orita H, Kobayashi T, Mizuguchi K, Endo M, Inoue I, Sato K, Yokomizo T
    • Journal Title

      Disease Markers

      Volume: - Pages: 1-7

    • DOI

      10.1155/2018/5280736

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] No novel, high penetrant gene might remain to be found in Japanese patients with unknown MODY2018

    • Author(s)
      Horikawa Y, Hosomichi K, Ishiura H, Suzuki Y, Tsuji S, Inoue I, Takeda J
    • Journal Title

      Journal of Human Genetics

      Volume: 印刷中 Issue: 7 Pages: 821-829

    • DOI

      10.1038/s10038-018-0449-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple common and rare variants of ABCG2 cause gout2017

    • Author(s)
      Higashino Toshihide、Takada Tappei、Nakaoka Hirofumi、Toyoda Yu、Stiburkova Blanka、Miyata Hiroshi、Ikebuchi Yuki、Nakashima Hiroshi、Shimizu Seiko、Kawaguchi Makoto、Sakiyama Masayuki、Nakayama Akiyoshi、Akashi Airi、Tanahashi Yuki、Kawamura Yusuke、Nakamura Takahiro、Wakai Kenji、Hosomichi Kazuyoshi 他
    • Journal Title

      RMD Open

      Volume: 3 Issue: 2 Pages: e000464-e000464

    • DOI

      10.1136/rmdopen-2017-000464

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] AMBRA1 is involved in T cell receptor-mediated metabolic reprogramming through an ATG7-independent pathway2017

    • Author(s)
      Akatsuka Hisako、Kuga Shuhei、Masuhara Kaori、Davaadorj Odontuya、Okada Chisa、Iida Yumi、Okada Yoshinori、Fukunishi Nahoko、Suzuki Takahiro、Hosomichi Kazuyoshi、Ohtsuka Masato、Tanaka Masafumi、Inoue Ituro、Kimura Minoru、Sato Takehito
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 491 Issue: 4 Pages: 1098-1104

    • DOI

      10.1016/j.bbrc.2017.08.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung’s disease2017

    • Author(s)
      Kawano Takafumi、Hosomichi Kazuyoshi、Inoue Ituro、Shimono Ryuichi、Onishi Shun、Nakame Kazuhiko、Kaji Tatsuru、Matsufuji Hiroshi、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1041-1046

    • DOI

      10.1007/s00383-017-4134-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses2017

    • Author(s)
      Ito J, Sugimoto R, Nakaoka H, Yamada S, Kimura T, Hayano T, Inoue I.
    • Journal Title

      PLOS Genetics

      Volume: 13 Issue: 7 Pages: e1006883-e1006883

    • DOI

      10.1371/journal.pgen.1006883

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.2017

    • Author(s)
      Nakayama A, Nakaoka H, Yamamoto K, Sakiyama M, Shaukat A, Toyoda Y, Okada Y, Ohkawa Y,他39名
    • Journal Title

      Ann Rheum Dis.

      Volume: 76 Issue: 5 Pages: 869-877

    • DOI

      10.1136/annrheumdis-2016-209632

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy2017

    • Author(s)
      Watanabe H, Goto S, Mori H, Higashi K, Hosomichi K, Aizawa N, Takahashi N, Tsuchida M, Suzuki Y, Yamada T, Horii A, Inoue I, Kurokawa K, Narita I.
    • Journal Title

      Nephrol Dial Transplant

      Volume: in press Pages: 2072-2079

    • DOI

      10.1093/ndt/gfw343

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan.2017

    • Author(s)
      Kanzawa-Kiriyama H, Kryukov K, Jinam TA, Hosomichi K, Saso A, Suwa G, Ueda S, Yoneda M, Tajima A, Shinoda KI, Inoue I, Saitou N. A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan
    • Journal Title

      J Hum Genetics

      Volume: 印刷中 Issue: 2 Pages: 213-221

    • DOI

      10.1038/jhg.2016.110

    • NAID

      40021064864

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid and cost-effective high-throughput sequencing for identification of germline mutations of BRCA1 and BRCA22017

    • Author(s)
      Ahmadloo S, Nakaoka H, Hayano T, Hosomichi K, You H, Utsuno E, Sangai T, Nishimura M, Matsushita K, Hata A, Nomura F, Inoue I
    • Journal Title

      J Hum Genetics

      Volume: 印刷中 Issue: 5 Pages: 561-567

    • DOI

      10.1038/jhg.2017.5

    • NAID

      40021210379

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing2017

    • Author(s)
      Yamaguchi T, Hosomichi K, Yano K, Kim Y, Nakaoka H, Kimura R, Otsuka H, Nonaka N, Haga S, Takahashi M, Shirota T, Kikkawa Y, Yamada A, Kamijo R, Park SB, Nakamura M, Maki K, Inoue I
    • Journal Title

      Hum Genome Variation

      Volume: 印刷中 Issue: 1 Pages: 17005-17005

    • DOI

      10.1038/hgv.2017.5

    • NAID

      120006891152

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure and evolution of the filaggrin gene repeated region in primates2017

    • Author(s)
      Romero V, Hosomichi K, Nakaoka H, Shibata H, Inoue I
    • Journal Title

      BMC Evol Biol.

      Volume: 印刷中 Issue: 1 Pages: 10-10

    • DOI

      10.1186/s12862-016-0851-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Germline Variants of Prostate Cancer in Japanese Families2017

    • Author(s)
      Hayano T, Matsui H, Nakaoka H, Ohtake N, Hosomichi K, Suzuki K, Inoue I
    • Journal Title

      PLoS One

      Volume: 印刷中 Issue: 10 Pages: e0164233-e0164233

    • DOI

      10.1371/journal.pone.0164233

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.2016

    • Author(s)
      van 't Hof FN, Ruigrok YM, Lee CH, Ripke S, Anderson G, Wang GT; Aneurysm Consortium; Vascular Research Consortium of New Zealand, Han B, Rinkel GJ, de Bakker PI et al.
    • Journal Title

      J Am Heart Assoc

      Volume: 5 Issue: 7

    • DOI

      10.1161/jaha.115.002603

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus.2016

    • Author(s)
      M. Sakiyama, H. Matsuo, H. Nakaoka, K. Yamamoto, A. Nakayama, T. Nakamura, S. Kawai, R. Okada, H. Ooyama, T. Shimizu, and N. Shinomiya
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 25360-25360

    • DOI

      10.1038/srep25360

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.2016

    • Author(s)
      Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer WH, Yoshihara K, Yamamoto A, Kurose K, Enomoto T, Akira S, Hosomichi K,, Inoue I.
    • Journal Title

      PLoS Genet.

      Volume: 1 Issue: 4 Pages: 1-23

    • DOI

      10.1371/journal.pgen.1005893

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLAアレルからみた東アジア集団~旧人類との遺伝的混合2016

    • Author(s)
      中岡博史、井ノ上逸朗
    • Journal Title

      医学の歩み

      Volume: 258 Pages: 172-174

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Novel kinase fusion transcripts found in endometrial cancer.2015

    • Author(s)
      Tamura R, Yoshihara K, Yamawaki K, Suda K, Ishiguro T, Adachi S, Okuda S, Inoue I, Verhaak RG, Enomoto T.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 18657-18657

    • DOI

      10.1038/srep18657

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of novel exonic mobile element insertions in epithelial ovarian cancers.2015

    • Author(s)
      Hayano,T., Yamada,S., Hosomichi,K., Nakaoka,H., Yoshihara,K., Adachi.S. Kashima,K., Tanaka, K and Enomoto,T.& Inoue,I.
    • Journal Title

      Human Genome Variation

      Volume: 2 Issue: 1 Pages: 15030-15030

    • DOI

      10.1038/hgv.2015.30

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of next-generation sequencing technologies on HLA research.2015

    • Author(s)
      Hosomichi K, Shiina T, Tajima A, Inoue I.
    • Journal Title

      Journal of human genetics

      Volume: 60 Issue: 11 Pages: 665-673

    • DOI

      10.1038/jhg.2015.102

    • NAID

      40020655134

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of HLA haplotypes across Japanese Archipelago: similarity, difference and admixture.2015

    • Author(s)
      Nakaoka H, Inoue I.
    • Journal Title

      Journal of human genetics

      Volume: 60 Issue: 11 Pages: 683-690

    • DOI

      10.1038/jhg.2015.90

    • NAID

      40020655147

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unique characteristics of the Ainu population in Northern Japan2015

    • Author(s)
      Jinam TA, Kanzawa-Kiriyama H, Inoue I, Tokunaga K, Omoto K, Saitou N
    • Journal Title

      Journal of Human Genetics

      Volume: 60 Issue: 10 Pages: 565-571

    • DOI

      10.1038/jhg.2015.79

    • NAID

      40020621361

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients.2015

    • Author(s)
      Mitsunaga S, Hosomichi K, Okudaira Y, Nakaoka H, Suzuki Y, Kuwana M, Sato S, Kaneko Y, Homma Y, Oka A, Shiina T, Inoko H, Inoue I.
    • Journal Title

      J Hum Genet

      Volume: 60 Issue: 8 Pages: 449-454

    • DOI

      10.1038/jhg.2015.50

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 体細胞変異からの子宮内膜症の成因 その3 逆行仮説の検証2017

    • Author(s)
      井ノ上 逸朗
    • Organizer
      日本人類遺伝学会 第62回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Allelic imbalance in regulation of ANRIL through chromatin interaction at 9p21 endometriosis risk locus.2016

    • Author(s)
      Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer W, Hata C, Kimura T, Hosomichi K, Inoue I.
    • Organizer
      The American Society of Human Genetics 66th Annual Meeting
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-10-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.2016

    • Author(s)
      Ito J, Yamada S, Sugimoto R, Kimura T, Nakaoka H, Inoue I.
    • Organizer
      The American Society of Human Genetics 66th Annual Meeting
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-10-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Allelic imbalance in regulation of ANRIL through chromatin interaction at 9p21 endometriosis risk locus2016

    • Author(s)
      Hirofumi Nakaoka
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-04-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evolution of the ‘fused’ gene family across primates.2016

    • Author(s)
      Nakaoka H, Romero V, Inoue I, Hosomichi K.
    • Organizer
      The 13th International Congress of Human Genetics.
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-04-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Allelic imbalance in regulation of ANRIL through chromatin interaction at 9p21 endometriosis risk locus.2016

    • Author(s)
      Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer W, Hosomichi K, Inoue I.
    • Organizer
      The 13th International Congress of Human Genetics.
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-04-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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