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Profiling of conserved non-coding elements upstream of SHOX and functional characterisation of the SHOX cis-regulatory landscape

Hannah Verdin UGent, Ana Fernández-Miñán, Sara Benito-Sanz, Sandra Janssens, Bert Callewaert UGent, Kathleen De Waele, Jean De Schepper UGent, Inge François, Björn Menten UGent, Karen E Heath, et al. (2015) SCIENTIFIC REPORTS. 5.
abstract
Genetic defects such as copy number variations (CNVs) in non-coding regions containing conserved non-coding elements (CNEs) outside the transcription unit of their target gene, can underlie genetic disease. An example of this is the short stature homeobox (SHOX) gene, regulated by seven CNEs located downstream and upstream of SHOX, with proven enhancer capacity in chicken limbs. CNVs of the downstream CNEs have been reported in many idiopathic short stature (ISS) cases, however, only recently have a few CNVs of the upstream enhancers been identified. Here, we set out to provide insight into: (i) the cis-regulatory role of these upstream CNEs in human cells, (ii) the prevalence of upstream CNVs in ISS, and (iii) the chromatin architecture of the SHOX cis-regulatory landscape in chicken and human cells. Firstly, luciferase assays in human U2OS cells, and 4C-seq both in chicken limb buds and human U2OS cells, demonstrated cis-regulatory enhancer capacities of the upstream CNEs. Secondly, CNVs of these upstream CNEs were found in three of 501 ISS patients. Finally, our 4C-seq interaction map of the SHOX region reveals a cis-regulatory domain spanning more than 1 Mb and harbouring putative new cis-regulatory elements.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
TIME QUANTITATIVE PCR, PSEUDOAUTOSOMAL REGION 1, HOMEOBOX GENE SHOX, LANGER MESOMELIC DYSPLASIA, LERI-WEILL DYSCHONDROSTEOSIS, IDIOPATHIC SHORT STATURE, HUMAN GENOME, TURNER-SYNDROME, COPY NUMBER, CHROMOSOME CONFORMATION
journal title
SCIENTIFIC REPORTS
Sci. Rep.
volume
5
article number
17667
pages
9 pages
Web of Science type
Article
Web of Science id
000365701400001
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
5.228 (2015)
JCR rank
7/63 (2015)
JCR quartile
1 (2015)
ISSN
2045-2322
DOI
10.1038/srep17667
language
English
UGent publication?
yes
classification
A1
additional info
the last two authors jointly supervised this work
copyright statement
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
id
7083764
handle
http://hdl.handle.net/1854/LU-7083764
date created
2016-02-12 13:36:42
date last changed
2018-05-23 10:11:57
@article{7083764,
  abstract     = {Genetic defects such as copy number variations (CNVs) in non-coding regions containing conserved non-coding elements (CNEs) outside the transcription unit of their target gene, can underlie genetic disease. An example of this is the short stature homeobox (SHOX) gene, regulated by seven CNEs located downstream and upstream of SHOX, with proven enhancer capacity in chicken limbs. CNVs of the downstream CNEs have been reported in many idiopathic short stature (ISS) cases, however, only recently have a few CNVs of the upstream enhancers been identified. Here, we set out to provide insight into: (i) the cis-regulatory role of these upstream CNEs in human cells, (ii) the prevalence of upstream CNVs in ISS, and (iii) the chromatin architecture of the SHOX cis-regulatory landscape in chicken and human cells. Firstly, luciferase assays in human U2OS cells, and 4C-seq both in chicken limb buds and human U2OS cells, demonstrated cis-regulatory enhancer capacities of the upstream CNEs. Secondly, CNVs of these upstream CNEs were found in three of 501 ISS patients. Finally, our 4C-seq interaction map of the SHOX region reveals a cis-regulatory domain spanning more than 1 Mb and harbouring putative new cis-regulatory elements.},
  articleno    = {17667},
  author       = {Verdin, Hannah and Fern{\'a}ndez-Mi{\~n}{\'a}n, Ana and Benito-Sanz, Sara and Janssens, Sandra and Callewaert, Bert and De Waele, Kathleen and De Schepper, Jean and Fran\c{c}ois, Inge and Menten, Bj{\"o}rn and Heath, Karen E and G{\'o}mez-Skarmeta, Jos{\'e} Luis and De Baere, Elfride},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {TIME QUANTITATIVE PCR,PSEUDOAUTOSOMAL REGION 1,HOMEOBOX GENE SHOX,LANGER MESOMELIC DYSPLASIA,LERI-WEILL DYSCHONDROSTEOSIS,IDIOPATHIC SHORT STATURE,HUMAN GENOME,TURNER-SYNDROME,COPY NUMBER,CHROMOSOME CONFORMATION},
  language     = {eng},
  pages        = {9},
  title        = {Profiling of conserved non-coding elements upstream of SHOX and functional characterisation of the SHOX cis-regulatory landscape},
  url          = {http://dx.doi.org/10.1038/srep17667},
  volume       = {5},
  year         = {2015},
}

Chicago
Verdin, Hannah, Ana Fernández-Miñán, Sara Benito-Sanz, Sandra Janssens, Bert Callewaert, Kathleen De Waele, Jean De Schepper, et al. 2015. “Profiling of Conserved Non-coding Elements Upstream of SHOX and Functional Characterisation of the SHOX Cis-regulatory Landscape.” Scientific Reports 5.
APA
Verdin, H., Fernández-Miñán, A., Benito-Sanz, S., Janssens, S., Callewaert, B., De Waele, K., De Schepper, J., et al. (2015). Profiling of conserved non-coding elements upstream of SHOX and functional characterisation of the SHOX cis-regulatory landscape. SCIENTIFIC REPORTS, 5.
Vancouver
1.
Verdin H, Fernández-Miñán A, Benito-Sanz S, Janssens S, Callewaert B, De Waele K, et al. Profiling of conserved non-coding elements upstream of SHOX and functional characterisation of the SHOX cis-regulatory landscape. SCIENTIFIC REPORTS. 2015;5.
MLA
Verdin, Hannah, Ana Fernández-Miñán, Sara Benito-Sanz, et al. “Profiling of Conserved Non-coding Elements Upstream of SHOX and Functional Characterisation of the SHOX Cis-regulatory Landscape.” SCIENTIFIC REPORTS 5 (2015): n. pag. Print.