Evidence map›Paper›PMID 42014869›Full record

ArticleNature metabolism2026

A conserved hormonal signalling-H2A.Z axis rapidly reorganizes 3D chromatin interactions in adipocyte thermogenesis.

Yang Zhang, Rongbin Zheng, Tadataka Tsuji, Chih-Hao Wang, Xiang-Yu Liu, Yu-Hang Xing, Justin Darcy, Matthew D Lynes, Morten Lundh, Rini Arianti and 9 more

Abstract read
In one paragraph

Article in Nature metabolism, 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

19 authors.

Yang Zhang *Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Rongbin Zheng *Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.
Tadataka TsujiSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2837-8246
Chih-Hao WangSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Xiang-Yu LiuSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Yu-Hang XingBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0525-4248
Justin DarcySection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Matthew D LynesSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Morten LundhSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Rini AriantiLaboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.ORCID http://orcid.org/0000-0002-0525-4902
Ferenc GyőryDepartment of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Rui DongBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brice EmanuelliNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5795-5666
Sarah E JohnstoneBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Miguel N RiveraBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Endre KristófLaboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.ORCID http://orcid.org/0000-0002-2215-6984
C Ronald KahnSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7583-9228
Kaifu ChenBasic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA. kaifu.chen@childrens.harvard.edu.ORCID http://orcid.org/0000-0003-1009-4357
Yu-Hua TsengSection on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. yu-hua.tseng@joslin.harvard.edu.ORCID http://orcid.org/0000-0003-2053-9559

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Fibroblast Growth Factor and Energy MetabolismR01DK102898 · NIDDK · JOSLIN DIABETES CENTER · PI TSENG, YU-HUA · 2015 to 2024
$4.1M
Transcriptional and epigenetic regulation of thermogenic adipocyte programR01DK132469 · NIDDK · JOSLIN DIABETES CENTER · PI Yu-Hua Tseng · 2022 to 2026
$3.0M
Reversal of Heart Failure: Role of Vascular RecoveryR01HL148338 · NHLBI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHEN, KAIFU, COOKE, JOHN P · 2020 to 2023
$2.8M
Dissecting the thermogenic adipose nicheR01DK133528 · NIDDK · JOSLIN DIABETES CENTER · PI TSENG, YU-HUA · 2022 to 2025
$2.8M
A novel role for EZH2 in A-to-I RNA editing in prostate cancerR01CA278832 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Qi Cao, Kaifu Chen · 2024 to 2026
$2.0M
Bioinformatics Techniques to Analyze Dynamic Changes of 3D GenomeR01GM138407 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI CHEN, KAIFU · 2022 to 2025
$1.8M
Role of S-nitrosylation in TransdifferentiationR01HL133254 · NHLBI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHEN, KAIFU, COOKE, JOHN P · 2018 to 2021
$1.6M
Computational epigenetics modeling of cell identity genesR01GM125632 · NIGMS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHEN, KAIFU · 2018 to 2021
$1.4M
Small Animal High Resolution Metabolic Analysis SystemS10OD028568 · OD · JOSLIN DIABETES CENTER · PI TSENG, YU-HUA · 2020 to 2020
$573k
Computational Technology for Single-Cell Functional GenomicsK99HG013662 · NHGRI · BOSTON CHILDREN'S HOSPITAL · PI Rongbin Zheng · 2025 to 2026
$261k
NCI NIH HHS R01 CA278832NHGRI NIH HHS K99 HG013662NHLBI NIH HHS R01 HL133254NHLBI NIH HHS R01 HL148338NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK102898NIDDK NIH HHS R01 DK132469NIDDK NIH HHS R01 DK133528NIGMS NIH HHS R01 GM125632NIGMS NIH HHS R01 GM138407NIH HHS S10 OD028568U.S. Department of Health & Human Services | National Institutes of Health (NIH) K99HG013662U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30DK036836U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA278832U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK102898U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK132469U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK133528U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM125632U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM138407U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL133254U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HL148338U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD028568
6 · The paper itself

Abstract

Three-dimensional genome organization underlies gene regulation, yet how acute hormonal signalling reshapes chromatin structure to control metabolism remains unclear. β3-adrenergic receptor (β3-AR) hormonal signalling drives adipocyte thermogenesis. Here, we show three-dimensional genome maps of mouse and primary human brown adipocytes during thermogenesis using Micro-C. We find that β3-AR signalling rapidly reorganizes chromatin loops within 4 h, with dynamically gained loops coupled to thermogenic gene activation in both species. Mechanistically, β3-AR stimulation promotes histone variant H2A.Z deposition to enhance chromatin accessibility at loop anchors, facilitating the recruitment of bridging factor MED1. Loss of H2A.Z compromises loop formation and thermogenic gene activation across species. Brown fat-specific H2A.Z deficiency in mice impairs thermogenic activity and glucose tolerance. Integration with genome-wide association studies links H2A.Z-occupied loops to genetic variants associated with obesity and related metabolic disorders. Together, our findings uncover a cross-species conserved β3-AR signalling-H2A.Z axis that rapidly reorganizes chromatin interactions in adipocyte thermogenesis, providing mechanistic and translational insights into metabolic regulation.

Indexed as

AdipocytesChromatinHistonesReceptors, Adrenergic, beta-3Signal TransductionThermogenesisAdipocytes, BrownAnimalsHumansMiceChromatinHistonesReceptors, Adrenergic, beta-3

Identifiers

PMID42014869
PMCPMC13218939

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.