Imperial College London
Alternate

ProfessorRichardFestenstein

Faculty of Medicine, Department of Brain Sciences

Clinical Professor of Molecular Medicine
 
 
 
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Contact

 

+44 (0)20 3313 8310r.festenstein

 
 
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Assistant

 

Ms Hyacinth Henry +44 (0)20 3313 3172

 
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Location

 

London Institute of Medical Sciences, Mansfield BuildingNeptune BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tam:2016:nar/gkw820,
author = {Tam, KT and Chan, PK and Zhang, W and Law, PP and Tian, Z and Fung, Chan GC and Philipsen, S and Festenstein, R and Tan-Un, KC},
doi = {nar/gkw820},
journal = {Nucleic Acids Research},
pages = {115--126},
title = {Identification of a novel distal regulatory element of the human Neuroglobin gene by the chromosome conformation capture approach},
url = {http://dx.doi.org/10.1093/nar/gkw820},
volume = {45},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Neuroglobin (NGB) is predominantly expressed in the brain and retina. Studies suggest that NGB exerts protective effects to neuronal cells and is implicated in reducing the severity of stroke and Alzheimer's disease. However, little is known about the mechanisms which regulate the cell type-specific expression of the gene. In this study, we hypothesized that distal regulatory elements (DREs) are involved in optimal expression of the NGB gene. By chromosome conformation capture we identified two novel DREs located -70 kb upstream and +100 kb downstream from the NGB gene. ENCODE database showed the presence of DNaseI hypersensitive and transcription factors binding sites in these regions. Further analyses using luciferase reporters and chromatin immunoprecipitation suggested that the -70 kb region upstream of the NGB gene contained a neuronal-specific enhancer and GATA transcription factor binding sites. Knockdown of GATA-2 caused NGB expression to drop dramatically, indicating GATA-2 as an essential transcription factor for the activation of NGB expression. The crucial role of the DRE in NGB expression activation was further confirmed by the drop in NGB level after CRISPR-mediated deletion of the DRE. Taken together, we show that the NGB gene is regulated by a cell type-specific loop formed between its promoter and the novel DRE.
AU  - Tam,KT
AU  - Chan,PK
AU  - Zhang,W
AU  - Law,PP
AU  - Tian,Z
AU  - Fung,Chan GC
AU  - Philipsen,S
AU  - Festenstein,R
AU  - Tan-Un,KC
DO  - nar/gkw820
EP  - 126
PY  - 2016///
SN  - 1362-4962
SP  - 115
TI  - Identification of a novel distal regulatory element of the human Neuroglobin gene by the chromosome conformation capture approach
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkw820
UR  - http://hdl.handle.net/10044/1/40845
VL  - 45
ER  -
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