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DOI | 10.1242/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
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ISSN | 0950-1991 |
EISSN | 1477-9129 |
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 |
推荐引用方式 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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