NDLI: Mapping the Shh long-range regulatory domain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Anderson, Eve Devenney, Paul S. Hill, Robert E. Lettice, Laura A.
Description	Country affiliation: United kingdom Author Affiliation: Anderson E ( MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.); Devenney PS ( MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.); Hill RE ( MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK bob.hill@igmm.ed.ac.uk.); Lettice LA ( MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.)
Abstract	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 900âkb 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.
File Format	HTM / HTML
ISSN	09501991
e-ISSN	14779129
DOI	10.1242/dev.108480
Journal	Development
Issue Number	20
Volume Number	141
Language	English
Publisher	The Company of Biologists
Publisher Date	2014-10-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Developmental Discipline Biology Gene Expression Regulation, Developmental Hedgehog Proteins Physiology Animals Blastocyst Cytology Dna Transposable Elements Enhancer Elements, Genetic Gene Expression Profiling Genes, Reporter Genetic Complementation Test Genetics Heterozygote Introns Mice Mice, Transgenic Models, Genetic Promoter Regions, Genetic Protein Structure, Tertiary Transgenes Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Molecular Biology

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