Evidence map›Paper›PMID 42462028›Full record

ArticleScience (New York, N.Y.)2026

A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin.

Alex C Sternisha, Haocheng Li, Kumar Gajendra, Yi Xiao, Xin Zhao, Jeffrey I Traylor, Lei Guo, Ji Hyung Jun, Morgan Fleishman, Tracey Shipman and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

34 authors.

Alex C Sternisha *Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-0771-6725
Haocheng Li *Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0001-9237-7520
Kumar GajendraDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Yi XiaoChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-3817-3471
Xin ZhaoChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jeffrey I TraylorChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1749-8143
Lei GuoQuantitative Biomedical Research Center, Department of Health Science & Biostatistics, Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ji Hyung JunChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2563-4144
Morgan FleishmanDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Tracey ShipmanChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0009-0004-4497-7080
Vinesh T PuliyappadambaChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-2284-4362
Pranita KaphleChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Qing OuyangDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.ORCID 0000-0003-1062-1321
Michael SchmidtDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.ORCID 0000-0002-7990-033X
Diana D ShiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Milan R SavaniChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1776-451X
Alexander C-Y TsaiDepartment of Radiation Oncology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
Joyce H LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8264-9625
Ruth GordilloTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-6533-2493
Javier Garcia-BermudezChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-5274-7040
Yoon Jung KimChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2942-294X
Shih-Chia TsoDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chad A BrautigamDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-6563-1338
Lauren G ZachariasChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Thomas P MathewsChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-9355-8243
Lin XuHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-5815-4457
John G DoenchBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-3707-9889
Vidyasagar KoduriDivision of Hematology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9700-8169
Kalil G AbdullahDepartment of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-5662-0829
Michalis AgathocleousChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Laura A BanaszynskiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-5189-8848
Ralph J DeBerardinisChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2705-7432
Eric M MorrowDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.ORCID 0000-0003-3430-3520
Samuel K McBrayerChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-9361-675X

Funding

Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5M
Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
Pathogenic Mechanisms in Christianson Syndrome and NHE6-Related DisordersR01NS113141 · NINDS · BROWN UNIVERSITY · PI Eric M Morrow · 2019 to 2026
$7.0M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Michelle Monje-Deisseroth · 2021 to 2026
$6.4M
Chromatin Dynamics and Genome RegulationR35GM124958 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2017 to 2026
$4.4M
Mechanisms of Disease and Treatments in Novel Metabolic Development Brain DisordersR01NS121618 · NINDS · BROWN UNIVERSITY · PI Eric M Morrow · 2022 to 2026
$3.2M
Metabolic Mechanisms in Locus Coeruleus Neuron Vulnerability in Neurodegenerative DiseaseR01AG087455 · NIA · BROWN UNIVERSITY · PI Eric M Morrow · 2024 to 2026
$2.3M
Mechanisms of p300 Activation During Pluripotency and Differentiation.R01HD109239 · NICHD · UT SOUTHWESTERN MEDICAL CENTER · PI Laura Banaszynski · 2022 to 2026
$2.1M
Exploiting Pyrimidine Nucleotide Synthesis Dependence for IDH Mutant Glioma TherapyR01CA258586 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI ABDULLAH, KALIL G, MCBRAYER, SAMUEL KENT · 2021 to 2025
$1.8M
Development of a nuclear alpha-ketoglutarate biosensor system to study metabolic control of the epigenomeR01GM158820 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI MCBRAYER, SAMUEL KENT · 2025 to 2025
$1.8M
The role of ascorbate in myelopoiesis and infectionR01DK125713 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI AGATHOCLEOUS, MICHALIS · 2021 to 2025
$1.8M
High-resolution approaches to dissect the role of subcellular redox circuits in vivoDP2GM159178 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI GARCIA BERMUDEZ, JAVIER · 2024 to 2024
$1.5M
NCI NIH HHS F30 CA271634NCI NIH HHS K12 CA090354NCI NIH HHS K99 CA277576NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA258586NCI NIH HHS R01 CA289260NCI NIH HHS U19 CA264504NIA NIH HHS R01 AG087455NICHD NIH HHS R01 HD109239NIDDK NIH HHS R01 DK125713NIDDK NIH HHS R01 DK145539NIGMS NIH HHS DP2 GM159178NIGMS NIH HHS R01 GM158820NIGMS NIH HHS R35 GM124958NINDS NIH HHS R01 NS113141NINDS NIH HHS R01 NS121618NINDS NIH HHS R01 NS142141
6 · The paper itself

Abstract

The metabolite α-ketoglutarate (αKG) is required for chromatin demethylation, but mechanisms that control αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metabolite pool in human cells using an αKG-responsive cyanobacterial transcription factor, NtcA, and used it to identify genes that regulate αKG in the nucleus. We defined an interorganelle pathway in which sequential mitochondrial activities of glutamic-pyruvic transaminase 2 (GPT2) and the SLC25A11 transporter supply nuclear αKG. In a mouse model of GPT2 deficiency, an inborn error of metabolism, Gpt2 loss caused histone hypermethylation in the brain and dysregulated neurodevelopmental genes. Restoring αKG counteracted these changes and promoted mouse fitness. Our work provides a tool to directly monitor nuclear αKG and reveals nuclear αKG depletion as a key pathogenic mechanism underlying GPT2 deficiency.

Indexed as

Biosensing TechniquesCell NucleusChromatinKetoglutaric AcidsTranscription, GeneticAnimalsBacterial ProteinsBrainHistonesHumansMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaSignal TransductionBacterial ProteinsChromatinHistonesKetoglutaric AcidsTransaminases

Identifiers

PMID42462028
PMCPMC13584912

What OpenQuestion holds

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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.