干旱区生态环境知识资源中心(Arid): Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs

Arid

DOI	10.1186/s13059-020-02059-3
	Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs
	Do, Catherine 1,2; Dumont, Emmanuel L. P.1,2; Salas, Martha 1,2; Castano, Angelica 1,2; Mujahed, Huthayfa 3; Maldonado, Leonel 4; Singh, Arunjot 5; DaSilva-Arnold, Sonia C.6; Bhagat, Govind 7,8; Lehman, Soren 3; Christiano, Angela M.9,10; Madhavan, Subha 11; Nagy, Peter L.12; Green, Peter H. R.8; Feinman, Rena 1,2,11; Trimble, Cornelia 4; Illsley, Nicholas P.6; Marder, Karen 13,14; Honig, Lawrence 13,14; Monk, Catherine 15,16; Goy, Andre 1,2,11; Chow, Kar 1,2,11; Goldlust, Samuel 1,2; Kaptain, George 1,2; Siegel, David 1,2,11; Tycko, Benjamin 1,2,11
通讯作者	Do, Catherine ; Tycko, Benjamin
来源期刊	GENOME BIOLOGY
ISSN	1474-760X
出版年	2020
卷号	21 期号:1
英文摘要	Background Mapping of allele-specific DNA methylation (ASM) can be a post-GWAS strategy for localizing regulatory sequence polymorphisms (rSNPs). The advantages of this approach, and the mechanisms underlying ASM in normal and neoplastic cells, remain to be clarified. Results We perform whole genome methyl-seq on diverse normal cells and tissues and three cancer types. After excluding imprinting, the data pinpoint 15,112 high-confidence ASM differentially methylated regions, of which 1838 contain SNPs in strong linkage disequilibrium or coinciding with GWAS peaks. ASM frequencies are increased in cancers versus matched normal tissues, due to widespread allele-specific hypomethylation and focal allele-specific hypermethylation in poised chromatin. Cancer cells show increased allele switching at ASM loci, but disruptive SNPs in specific classes of CTCF and transcription factor binding motifs are similarly correlated with ASM in cancer and non-cancer. Rare somatic mutations affecting these same motif classes track with de novo ASM. Allele-specific transcription factor binding from ChIP-seq is enriched among ASM loci, but most ASM differentially methylated regions lack such annotations, and some are found in otherwise uninformative chromatin deserts. Conclusions ASM is increased in cancers but occurs by a shared mechanism involving disruptive SNPs in CTCF and transcription factor binding sites in both normal and neoplastic cells. Dense ASM mapping in normal plus cancer samples reveals candidate rSNPs that are difficult to find by other approaches. Together with GWAS data, these rSNPs can nominate specific transcriptional pathways in susceptibility to autoimmune, cardiometabolic, neuropsychiatric, and neoplastic diseases.
类型	Article
语种	英语
国家	USA ; Sweden
开放获取类型	Green Published, Green Submitted, gold
收录类别	SCI-E
WOS记录号	WOS:000545942500001
WOS关键词	TRANSCRIPTION FACTOR-BINDING ; 5-METHYLCYTOSINE CONTENT ; WIDE ASSOCIATION ; CHROMATIN ; DIFFERENTIATION ; ELEMENTS ; MARKS ; IDENTIFICATION ; TROPHOBLAST ; METHYLOME
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/319555
作者单位	1.Hackensack Meridian Hlth Ctr Discovery & Innovat, Nutley, NJ 07110 USA; 2.Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ 07601 USA; 3.Karolinska Inst, Dept Med, SE-17177 Stockholm, Sweden; 4.Johns Hopkins Med Inst, Dept Gynecol & Obstet, Baltimore, MD 21287 USA; 5.Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA; 6.Hackensack Univ, Med Ctr, Dept Obstet & Gynecol, Hackensack, NJ 07601 USA; 7.Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA; 8.Columbia Univ, Div Gastroenterol & Celiac Ctr, Dept Med, Med Ctr, New York, NY 10032 USA; 9.Columbia Univ, Med Ctr, Dept Dermatol, New York, NY 10032 USA; 10.Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA; 11.Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA; 12.MNG Labs, Atlanta, GA 30342 USA; 13.Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA; 14.Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA; 15.Columbia Univ, Med Ctr, Dept Psychiat & Behav Med, New York, NY 10032 USA; 16.Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10032 USA
推荐引用方式 GB/T 7714	Do, Catherine,Dumont, Emmanuel L. P.,Salas, Martha,et al. Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs[J],2020,21(1).
APA	Do, Catherine.,Dumont, Emmanuel L. P..,Salas, Martha.,Castano, Angelica.,Mujahed, Huthayfa.,...&Tycko, Benjamin.(2020).Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs.GENOME BIOLOGY,21(1).
MLA	Do, Catherine,et al."Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs".GENOME BIOLOGY 21.1(2020).