Identification of a novel distal regulatory element of the human Neuroglobin gene by the chromosome conformation capture approach.

Autor:	Tam KT; School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China., Chan PK; Gene Control Mechanisms and Disease Group, Department of Medicine, Division of Brain Sciences and MRC Clinical Sciences Centre, Imperial College School of Medicine, London W12 0NN, United Kingdom., Zhang W; School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China., Law PP; School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.; Gene Control Mechanisms and Disease Group, Department of Medicine, Division of Brain Sciences and MRC Clinical Sciences Centre, Imperial College School of Medicine, London W12 0NN, United Kingdom.; Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China., Tian Z; School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.; School of Professional and Continuing Education (HKU SPACE), The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China., Fung Chan GC; Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China., Philipsen S; Department of Cell Biology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands kctanun@hkucc.hku.hk., Festenstein R; Gene Control Mechanisms and Disease Group, Department of Medicine, Division of Brain Sciences and MRC Clinical Sciences Centre, Imperial College School of Medicine, London W12 0NN, United Kingdom kctanun@hkucc.hku.hk., Tan-Un KC; School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China kctanun@hkucc.hku.hk.; School of Professional and Continuing Education (HKU SPACE), The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2017 Jan 09; Vol. 45 (1), pp. 115-126. Date of Electronic Publication: 2016 Sep 19.
DOI:	10.1093/nar/gkw820
Abstrakt:	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. (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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