干旱区生态环境知识资源中心(Arid): The Crohn's disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells

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DOI	10.1371/journal.pone.0212850
	The Crohn's disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells
	Matthews, Stephen M.1,2; Eshelman, Melanie A.1,2; Berg, Arthur S.3; Koltun, Walter A.2; Yochum, Gregory S.1,2
通讯作者	Yochum, Gregory S.
来源期刊	PLOS ONE
ISSN	1932-6203
出版年	2019
卷号	14 期号:2
英文摘要	Crohn's disease (CD) is a debilitating inflammatory bowel disease (IBD) that arises from chronic inflammation in the gastrointestinal tract. Genome-wide association studies (GWAS) have identified over 200 single nucleotide polymorphisms (SNPs) that are associated with a predisposition for developing IBD. For the majority, the causal variant and target genes affected are unknown. Here, we investigated the CD-associated SNP rs6651252 that maps to a gene desert region on chromosome 8. We demonstrate that rs6651252 resides within a Wnt responsive DNA enhancer element (WRE) and that the disease associated allele augments binding of the TCF7L2 transcription factor to this region. Using CRISPR/Cas9 directed gene editing and epigenetic modulation, we find that the rs6651252 enhancer regulates expression of the c-MYC proto-oncogene (MYC). Furthermore, we found MYC transcript levels are elevated in patient-derived colonic segments harboring the disease-associated allele in comparison to those containing the ancestral allele. These results suggest that Wnt/MYC signaling contributes to CD pathogenesis and that patients harboring the disease-associated allele may benefit from therapies that target MYC or MYC-regulated genes.
类型	Article
语种	英语
国家	USA
开放获取类型	Green Published, gold, Green Submitted
收录类别	SCI-E
WOS记录号	WOS:000459709100148
WOS关键词	INFLAMMATORY-BOWEL-DISEASE ; LONG-RANGE INTERACTION ; C-MYC ; T-CELL ; WNT ; TARGET ; RISK ; PATHOGENESIS ; ELEMENT ; LOCI
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/218087
作者单位	1.Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA; 2.Penn State Univ, Coll Med, Dept Surg, Div Colon & Rectal Surg, Hershey, PA 17033 USA; 3.Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA
推荐引用方式 GB/T 7714	Matthews, Stephen M.,Eshelman, Melanie A.,Berg, Arthur S.,et al. The Crohn's disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells[J],2019,14(2).
APA	Matthews, Stephen M.,Eshelman, Melanie A.,Berg, Arthur S.,Koltun, Walter A.,&Yochum, Gregory S..(2019).The Crohn's disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells.PLOS ONE,14(2).
MLA	Matthews, Stephen M.,et al."The Crohn's disease associated SNP rs6651252 impacts MYC gene expression in human colonic epithelial cells".PLOS ONE 14.2(2019).