Evidence map›Paper›PMID 29126261›Full record

ArticleNucleic acids research2018

Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family.

Sneha Lal, Jonathan M Comer, Purna C Konduri, Ajit Shah, Tianyuan Wang, Anthony Lewis, Grant Shoffner, Feng Guo, Li Zhang

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Antioxidants (Basel, Switzerland) · 2022
    Article
  4. Review
  5. Article
  6. The Multifaceted Role of Heme in Cancer.Frontiers in oncology · 2019
    Review
  7. Review
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 1 country.

Sneha LalDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
Jonathan M ComerDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
Purna C KonduriDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
Ajit ShahDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA.
Tianyuan WangDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
Anthony LewisDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
Grant ShoffnerDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Feng GuoDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Li ZhangDepartment of Biological Sciences, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, USA.
The University of Texas at Dallas · USUniversity of California, Los Angeles · USUniversity of California, San Francisco · US

Funding

Molecular Mechanism Governing Oxygen Signaling and Heme Regulation by Gis1R15GM107717 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI ZHANG, LI · 2014 to 2015
$411k
NIGMS NIH HHS R15 GM107717
6 · The paper itself

Abstract

The yeast Gis1 protein is a transcriptional regulator belonging to the JMJD2/KDM4 subfamily of demethylases that contain a JmjC domain, which are highly conserved from yeast to humans. They have important functions in histone methylation, cellular signaling and tumorigenesis. Besides serving as a cofactor in many proteins, heme is known to directly regulate the activities of proteins ranging from transcriptional regulators to potassium channels. Here, we report a novel mechanism governing heme regulation of Gis1 transcriptional and histone demethylase activities. We found that two Gis1 modules, the JmjN + JmjC domain and the zinc finger (ZnF), can bind to heme specifically in vitro. In vivo functional analysis showed that the ZnF, not the JmjN + JmjC domain, promotes heme activation of transcriptional activity. Likewise, measurements of the demethylase activity of purified Gis1 proteins showed that full-length Gis1 and the JmjN + JmjC domain both possess demethylase activity. However, heme potentiates the demethylase activity of full-length Gis1, but not that of the JmjN + JmjC domain, which can confer heme activation of transcriptional activity in an unrelated protein. These results demonstrate that Gis1 represents a novel class of multi-functional heme sensing and signaling proteins, and that heme binding to the ZnF stimulates Gis1 demethylase and transcriptional activities.

Indexed as

Signal TransductionTranscription, GeneticEnzyme ActivationHemeHistone DemethylasesJumonji Domain-Containing Histone DemethylasesProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsGIS1 protein, S cerevisiaeHemeHistone DemethylasesJumonji Domain-Containing Histone DemethylasesSaccharomyces cerevisiae Proteins

Identifiers

PMID29126261
PMCPMC5758875
OpenAlexW2767918730

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.