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한양대학교, 국립보건연구원
조회 1258  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Genetic factors underlying discordance in chromatin accessibility between monozygotic twins

Kwoneel Kim1,† Hyo-Jeong Ban2,3,† Jungmin Seo4 Kibaick Lee1 Maryam Yavartanoo1 Sang Cheol Kim5 Kiejung Park2 Seong Beom Cho2* and Jung Kyoon Choi1*

1 Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Republic of Korea
2 Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC, Choongchung-Buk-do 363-951, Republic of Korea
3 Division of Molecular and Life Sciences, Hanyang University, Ansan, Gyeonggi-do 425-791, Republic of Korea
4 Research Institute of Bioinformatics, Omicsis, Inc., Daejeon 305-333, Republic of Korea
5 Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Republic of Korea
Equal contributors.

* Corresponding author : Seong Beom Cho, Jung Kyoon Choi

Abstract
Background
Open chromatin is implicated in regulatory processes; thus, variations in chromatin structure may contribute to variations in gene expression and other phenotypes. In this work, we perform targeted deep sequencing for open chromatin, and array-based genotyping across the genomes of 72 monozygotic twins to identify genetic factors regulating co-twin discordance in chromatin accessibility.

Results
We show that somatic mutations cause chromatin discordance mainly via the disruption of transcription factor binding sites. Structural changes in DNA due to C:G to A:T transversions are under purifying selection due to a strong impact on chromatin accessibility. We show that CpGs whose methylation is specifically regulated during cellular differentiation appear to be protected from high mutation rates of 5[prime]-methylcytosines, suggesting that the spectrum of CpG variations may be shaped fully at the developmental level but not through natural selection. Based on the association mapping of within-pair chromatin differences, we search for cases in which twin siblings with a particular genotype had chromatin discordance at the relevant locus. We identify 1,325 chromatin sites that are differentially accessible, depending on the genotype of a nearby locus, suggesting that epigenetic differences can control regulatory variations via interactions with genetic factors. Poised promoters present high levels of chromatin discordance in association with either somatic mutations or genetic-epigenetic interactions.

Conclusion
Our observations illustrate how somatic mutations and genetic polymorphisms may contribute to regulatory, and ultimately phenotypic, discordance.

논문정보
- 형식: Research article
- 게재일: 2014년 05월 (BRIC 등록일 2014-06-02)
- 연구진: 국내연구진태극기
- 분야: Biotechnology, Genetics
세포 형광 이미징 멀티플렉싱을 위한 초고속 사이클링[Angew. Chem.-Int. Edit.]
고진아
발표: 고진아 (Massachusetts General Ho...)
일자: 2020년 4월 14일 (화) 오전 10시 (한국시간)
언어: 영어
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발표: 구민정 (University College Londo...)
일자: 2020년 4월 20일 (월) 오후 04시 (한국시간)
언어: 영어
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[BRIC Webinar]The presenting symptoms of cancer and stage at diagnosis[Lancet Oncol.]
[BRIC Webinar]The presenting symptoms of cancer and stage at diagnosis[Lancet Oncol.]
사전접수: ~2020.04.20
날짜: 2020.04.20
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[BRIC Webinar]세포 형광 이미징 멀티플렉싱을 위한 초고속 사이클링[Angew. Chem.-Int. Edit.]
[재직자무료교육] 분석기기(HPLC) 활용 품질검사 실습(4.9~4.10) / 화장품 제형제조 기술 실습(4.13~4.14)
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날짜: 2020.04.09~14
장소: 충청북도 청주시 흥덕구 오송읍 오송생명1로 194-41 충북산학융합본부 기업연구1관 교육장
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