Arid
DOI10.1242/dev.108480
Mapping the Shh long-range regulatory domain
Anderson, Eve; Devenney, Paul S.; Hill, Robert E.; Lettice, Laura A.
通讯作者Hill, Robert E.
来源期刊DEVELOPMENT
ISSN0950-1991
EISSN1477-9129
出版年2014
卷号141期号:20页码:3934-3943
英文摘要

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains.


英文关键词Sonic hedgehog (Shh) Enhancers Long-range regulation Topological domains Sleeping beauty transposon Mouse
类型Article
语种英语
国家Scotland
收录类别SCI-E
WOS记录号WOS:000343419600012
WOS关键词CIS-ACTING REGULATOR ; SONIC-HEDGEHOG ; EXPRESSION ; LIMB ; IDENTIFICATION ; TRANSCRIPTION ; ORGANIZATION ; LANDSCAPE ; DEFINES ; GENOME
WOS类目Developmental Biology
WOS研究方向Developmental Biology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/181563
作者单位Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland
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GB/T 7714
Anderson, Eve,Devenney, Paul S.,Hill, Robert E.,et al. Mapping the Shh long-range regulatory domain[J],2014,141(20):3934-3943.
APA Anderson, Eve,Devenney, Paul S.,Hill, Robert E.,&Lettice, Laura A..(2014).Mapping the Shh long-range regulatory domain.DEVELOPMENT,141(20),3934-3943.
MLA Anderson, Eve,et al."Mapping the Shh long-range regulatory domain".DEVELOPMENT 141.20(2014):3934-3943.
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