干旱区生态环境知识资源中心(Arid): Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction

Arid

DOI	10.7554/eLife.56697
	Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction
	van Weerd, Jan Hendrik; Mohan, Rajiv A.; van Duijvenboden, Karel; Hooijkaas, Ingeborg B.; Wakker, Vincent; Boukens, Bastiaan J.; Barnett, Phil; Christoffels, Vincent M.
通讯作者	Christoffels, VM
来源期刊	ELIFE
ISSN	2050-084X
出版年	2020
卷号	9
英文摘要	Genome-wide association studies have implicated common genomic variants in the gene desert upstream of TBX3 in cardiac conduction velocity. Whether these noncoding variants affect expression of TBX3 or neighboring genes and how they affect cardiac conduction is not understood. Here, we use high-throughput STARR-seq to test the entire 1.3 Mb human and mouse TBX3 locus, including two cardiac conduction-associated variant regions, for regulatory function. We identified multiple accessible and functional regulatory DNA elements that harbor variants affecting their activity. Both variant regions drove gene expression in the cardiac conduction tissue in transgenic reporter mice. Genomic deletion from the mouse genome of one of the regions caused increased cardiac expression of only Tbx3, PR interval shortening and increased QRS duration. Combined, our findings address the mechanistic link between trait-associated variants in the gene desert, TBX3 regulation and cardiac conduction.
类型	Article
语种	英语
开放获取类型	DOAJ Gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000551499100001
WOS关键词	TRANSCRIPTION FACTOR TBX3 ; GENOME-WIDE ASSOCIATION ; FACTOR-DNA-BINDING ; QRS DURATION ; ENHANCERS ; EXPRESSION ; CHROMATIN ; HEART ; LIMB ; INFORMATION
WOS类目	Biology
WOS研究方向	Life Sciences & Biomedicine - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/325154
作者单位	[van Weerd, Jan Hendrik; Mohan, Rajiv A.; van Duijvenboden, Karel; Hooijkaas, Ingeborg B.; Wakker, Vincent; Boukens, Bastiaan J.; Barnett, Phil; Christoffels, Vincent M.] Univ Amsterdam, Amsterdam Cardiovasc Sci, Dept Med Biol, Amsterdam Univ,Med Ctr, Amsterdam, Netherlands; [Mohan, Rajiv A.; Boukens, Bastiaan J.] Univ Amsterdam, Amsterdam Cardiovasc Sci, Dept Clin & Expt Cardiol, Amsterdam Univ,Med Ctr, Amsterdam, Netherlands
推荐引用方式 GB/T 7714	van Weerd, Jan Hendrik,Mohan, Rajiv A.,van Duijvenboden, Karel,et al. Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction[J],2020,9.
APA	van Weerd, Jan Hendrik.,Mohan, Rajiv A..,van Duijvenboden, Karel.,Hooijkaas, Ingeborg B..,Wakker, Vincent.,...&Christoffels, Vincent M..(2020).Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction.ELIFE,9.
MLA	van Weerd, Jan Hendrik,et al."Trait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction".ELIFE 9(2020).