Evidence map›Paper›PMID 41678541›Full record

ArticlePLoS biology2026

Integrated chromatin and transcriptomic profiling reveals sex-specific mechanisms of gene regulation in hepatic nutrient responses.

Zhengyi Zhang, Vivien Su, Carrie B Wiese, Lijing Cheng, Dan Wang, Ya Cui, Aneesh Kallapur, Jason Kim, Xiaohui Wu, Peter H Tran and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 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

16 authors.

Zhengyi ZhangDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID https://orcid.org/0000-0001-9094-1223
Vivien SuDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Carrie B WieseHuman Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Lijing ChengDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Dan WangDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Ya CuiDivision of Computational Biomedicine, Biological Chemistry, University of California, Irvine, Irvine, California, United States of America.
Aneesh KallapurDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Jason KimDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Xiaohui WuDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Peter H TranDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Zhenqi ZhouDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
David CaseroF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Wei LiDivision of Computational Biomedicine, Biological Chemistry, University of California, Irvine, Irvine, California, United States of America.
Andrea L HevenerDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Karen ReueMolecular Biology Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Tamer SallamDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID https://orcid.org/0000-0001-7144-7393

Funding

The impact of estrogen receptor alpha on cardiomyocellular metabolism and healthU54HL170326 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Hooman Allayee · 2023 to 2026
$7.5M
A sex-biased obesity gene on the X chromosomeR01DK143368 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Karen Reue · 2024 to 2026
$1.6M
NHLBI NIH HHS U54 HL170326NIDDK NIH HHS R01 DK143368
6 · The paper itself

Abstract

Little is known about how sex and diet interact at the level of chromatin organization. A comprehensive analysis of diet-induced chromatin dynamics can reveal how the liver mounts a rapid adaptive response to environmental cues and uncover mechanisms underlying sex differences. Here, we employed an integrative strategy to construct a nucleosome accessibility atlas of the mouse liver under different dietary conditions. Stringent analysis revealed a largely preserved hepatic chromatin landscape across feeding states, with sex being the critical factor driving changes in chromatin accessibility. Notably, lipid-rich diet preferentially enriched CCAAT-binding motifs in females, while nutrient-sensing nuclear receptor motifs were more strongly enriched in males. Furthermore, using the Four Core Genotypes model (XX ovaries / XY testes / XX testes / XY ovaries), we disentangled the effects of gonadal and chromosomal sex on diet-induced gene regulation. By leveraging this framework with multiple mouse models and molecular approaches, we identified a suppressive role of testosterone in regulating the sex-dimorphic GWAS gene PNPLA3. Overall, we establish an unbiased transcriptomic resource that revealed chromatin dynamics and identified gene clusters associated with distinct sex-related factors.

Indexed as

ChromatinGene Expression RegulationLiverAnimalsDietFemaleGene Expression ProfilingMaleMiceMice, Inbred C57BLNutrientsSex CharacteristicsTestosteroneTranscriptomeChromatinTestosterone

Identifiers

PMID41678541
PMCPMC12900309

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.