Evidence map›Paper›PMID 27651453›Full record

ArticleNucleic acids research2017

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

Kin Tung Tam, Ping Kei Chan, Wei Zhang, Pui Pik Law, Zhipeng Tian, Godfrey Chi Fung Chan, Sjaak Philipsen, Richard Festenstein, Kian Cheng Tan-Un

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. CRISPR Activator Approaches to Study Endogenous Androglobin Gene Regulation.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. CRISPR-based strategies for studying regulatory elements and chromatin structure in mammalian gene control.Mammalian genome : official journal of the International Mammalian Genome Society · 2018
    Review
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Kin Tung TamSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Ping Kei ChanGene 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.
Wei ZhangSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Pui Pik LawSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Zhipeng TianSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Godfrey Chi Fung ChanDepartment of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China.
Sjaak PhilipsenDepartment of Cell Biology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands kctanun@hkucc.hku.hk.
Richard FestensteinGene 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.
Kian Cheng Tan-UnSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong S.A.R., China kctanun@hkucc.hku.hk.
University of Hong Kong · HKErasmus MC · NLMRC Clinical Trials Unit at UCL · GB

Funding

Medical Research Council
6 · The paper itself

Abstract

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.

Indexed as

Regulatory Elements, TranscriptionalBinding SitesCell Line, TumorChromosomes, Human, Pair 14CRISPR-Cas SystemsDeoxyribonuclease IGATA2 Transcription FactorGene EditingGene Expression RegulationGenes, ReporterGlobinsHeLa CellsHumansK562 CellsLuciferasesNerve Tissue ProteinsDeoxyribonuclease IGATA2 protein, humanGATA2 Transcription FactorGlobinsLuciferasesNerve Tissue ProteinsNeuroglobinRNA, Guide, CRISPR-Cas SystemsRNA, Small Interfering

Identifiers

PMID27651453
PMCPMC5224503
OpenAlexW2523591699

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.