PMID- 25252942
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20220317
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 141
IP  - 20
DP  - 2014 Oct
TI  - Mapping the Shh long-range regulatory domain.
PG  - 3934-43
LID - 10.1242/dev.108480 [doi]
AB  - 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.
CI  - (c) 2014. Published by The Company of Biologists Ltd.
FAU - Anderson, Eve
AU  - Anderson E
AD  - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, 
      University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.
FAU - Devenney, Paul S
AU  - Devenney PS
AD  - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, 
      University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.
FAU - Hill, Robert E
AU  - Hill RE
AD  - 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.
FAU - Lettice, Laura A
AU  - Lettice LA
AD  - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, 
      University of Edinburgh, Crewe Rd, Edinburgh EH4 2XU, UK.
LA  - eng
GR  - MC_PC_U127584494/MRC_/Medical Research Council/United Kingdom
GR  - MC_U127584494/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140924
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (DNA Transposable Elements)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Shh protein, mouse)
SB  - IM
MH  - Animals
MH  - Blastocyst/cytology
MH  - DNA Transposable Elements
MH  - Enhancer Elements, Genetic
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Developmental
MH  - Genes, Reporter
MH  - Genetic Complementation Test
MH  - Hedgehog Proteins/genetics/*physiology
MH  - Heterozygote
MH  - Introns
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Genetic
MH  - Promoter Regions, Genetic
MH  - Protein Structure, Tertiary
MH  - Transgenes
PMC - PMC4197689
OTO - NOTNLM
OT  - Enhancers
OT  - Long-range regulation
OT  - Mouse
OT  - Sleeping beauty transposon
OT  - Sonic hedgehog (Shh)
OT  - Topological domains
EDAT- 2014/09/26 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/10/01
CRDT- 2014/09/26 06:00
PHST- 2014/09/26 06:00 [entrez]
PHST- 2014/09/26 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - dev.108480 [pii]
AID - DEV108480 [pii]
AID - 10.1242/dev.108480 [doi]
PST - ppublish
SO  - Development. 2014 Oct;141(20):3934-43. doi: 10.1242/dev.108480. Epub 2014 Sep 24.