Topics and Trends in Most Cited Epigenetics and DNA Methylation Papers

Ranked by citations 18 months after publication

Class of 2026 (Papers Published in 2024)

What topics and trends defined most-cited Epigenetics and DNA Methylation research in the Class of 2026?

Metabolism-linked epigenetics dominates the Class of 2026, with histone lactylation and metabolic reprogramming seeing massive increases. While foundational DNA methylation profiling remains central, the field is rapidly shifting toward understanding how metabolic states directly control epigenetic regulation in cancer and aging.

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Updated July 19, 2026

At a glance

Field
Epigenetics and DNA Methylation
Cohort label
Class of 2026 (2024 publications)
Papers analyzed
10,133
Papers ranked
20
Top topics in ranked papers
DNA methylation, Metabolic reprogramming, histone lactylation
Publication window
Jan 1, 2024 – Dec 31, 2024
Eligibility
Research articles; reviews excluded
Citation window
18 months post-publication
18m citation range
68–265
Data source
OpenAlex · Retrieved Jul 2026
License
CC BY 4.0

Rankings

20 papers ranked by 18-month citation count

#1 of 10,133
26518m citations

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla et al.Nature202410.1038/s41586-024-07019-6

Konstantinos HatzikotoulasUniversity of Manchester, United Kingdom

type 2 diabetes pathophysiologymulti-ancestry genome-wide association study1,289 independent association signals611 locieight non-overlapping clusterscardiometabolic trait associationscell-type-specific open chromatinpancreatic isletsadipocytesendothelial cellsenteroendocrine cellscluster-specific partitioned polygenic scorescoronary artery diseaseperipheral artery diseaseend-stage diabetic nephropathyobesity-related processessingle-cell epigenomicsaetiological heterogeneitygenetically informed diabetes care
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#2 of 10,133
20118m citations

Adipose tissue retains an epigenetic memory of obesity after weight loss

Laura C. Hinte et al.Nature202410.1038/s41586-024-08165-7

Ferdinand von MeyennLife Science Zurich Graduate School, Switzerland

epigenetic memoryAdipose tissueweight lossobesitysingle-nucleus RNA sequencingadipocytesobesogenic memoryrebound weight gainyo-yo effecthigh-fat dietTranscriptomic changesEpigenetic dysregulationmetabolic stimuli responsecellular memoryweight maintenanceadipocyte functionMouse model
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#3 of 10,133
16718m citations

Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma

Fei Li, Wenzhe Si, Li Xia et al.Molecular Cancer202410.1186/s12943-024-02008-9

Fei Li, Wenzhe Si, Li XiaPeking University Third Hospital, China

histone lactylationH3K18 lactylationPancreatic cancerglycolysisLDHAP300HDAC2TTK protein kinaseBUB1Bmitotic checkpoint regulatorsCUT&TagLDHA Y239 phosphorylationpositive feedback loopMetabolic reprogramminghistone writers and eraserslactate-dependent histone modificationglycolysis-H3K18la-TTK/BUB1B axis
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#4 of 10,133
16618m citations

H3K18 Lactylation Potentiates Immune Escape of Non–Small Cell Lung Cancer

Cai Zhang et al.Cancer Research202410.1158/0008-5472.can-23-3513

Cai ZhangThe First Affiliated Hospital of Zhengzhou University, China

H3K18 lactylationlysine lactylationnon-small cell lung cancerImmune evasionCD8+ T-cell cytotoxicityPD-L1POM121MYCglycolysis inhibition2-Deoxy-D-glucoseoxamateLDHAlactate dehydrogenase BCD274 promoteranti-PD-1 antibodytumor microenvironment remodelingMYC nuclear transportcombination immunotherapyMetabolic reprogramming
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#6 of 10,133
12318m citations

An epigenetic barrier sets the timing of human neuronal maturation

Christina S Leslie, Richard P Koche et al.Nature202410.1038/s41586-023-06984-8

Gabriele Ciceri, Lorenz StuderMemorial Sloan Kettering Cancer Center, United States

human neuronal maturation timingepigenetic barriercortical neuronsHuman pluripotent stem cellscell-intrinsic clocksynchronized neuronal birthmorphological and functional maturation atlasEZH2EHMT1EHMT2DOT1LEpigenetic primingtranscriptional poisingprogenitor cell programmingprecocious maturationHistone methyltransferasein vitro differentiationprotracted developmental timelinehPSC-derived cortical neurons
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#7 of 10,133
10918m citations

Transient loss of Polycomb components induces an epigenetic cancer fate

V Parreno, V Loubiere et al.Nature202410.1038/s41586-024-07328-w

Anne‐Marie Martinez, Giacomo CavalliCNRS, France

Polycomb group proteinsepigenetic cancer fateEpigenetic silencingnon-genetic tumorigenesisDrosophilaJAK-STAT signaling pathwayzfh1ZEB1 oncogeneirreversible gene derepressiontransient Polycomb perturbationEpigenetic dysregulationinheritance of altered cell fatescancer initiation without driver mutationsmalignant transformation
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#8 of 10,133
10618m citations

Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC

Yuanxiang Lu et al.Advanced Science202410.1002/advs.202401399

Jianping Zhao, Changzhen Shang, Huifang Liang, Wanguang ZhangHuazhong University of Science and Technology, China

lenvatinib resistancehepatocellular carcinomalysine lactylationIGF2BP3PCK2NRF2serine metabolism reprogrammingN6-methyladenosine (m6A) modificationS-adenosylmethionine (SAM)glycolysislactate accumulationantioxidant defense systemRNA m6A methylationlactylated IGF2BP3-PCK2-SAM-m6A loop2-Deoxy-D-glucosesiRNA targeting IGF2BP3liposome deliverymetabolic adaptationepigenetic remodelingmolecular-targeted therapy resistance
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#9 of 10,133
9918m citations

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer

Ningning Niu et al.Cancer Cell202410.1016/j.ccell.2024.03.005

Jing XueShanghai Jiao Tong University School of Medicine, China

tumor cell-intrinsic epigenetic dysregulationcancer-associated fibroblastsCAF heterogeneitymetabolic supportPancreatic cancerTumor-stroma crosstalkepigenetic reprogrammingfibroblast subpopulationsmetabolic couplingtumor microenvironment
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#10 of 10,133
9618m citations

scMD facilitates cell type deconvolution using single-cell DNA methylation references

Manqi Cai et al.Communications Biology202410.1038/s42003-023-05690-5

Jiebiao WangUniversity of Pittsburgh, United States

scMDCell type deconvolutionSingle-cell DNA methylationscDNAmbulk DNA methylation dataData sparsityultra-high dimensional datacell type fractionscell cluster aggregationcell-type marker DNAm sitescell-type signature matricessorted-cell referencesRNA-derived referencesAlzheimer's diseasecell type-specific differentially methylated cytosinesbrain tissuesolid tissues
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#11 of 10,133
9418m citations

ChIP-Atlas 3.0: a data-mining suite to explore chromosome architecture together with large-scale regulome data

Zhaonan Zou et al.Nucleic Acids Research202410.1093/nar/gkae358

Zhaonan ZouKumamoto University, Japan

ChIP-AtlasChIP-seqATAC-seqDNase-seqBisulfite-seqHi-CeQTLChromHMMFANTOM5 enhancersGWAS variantsClinVar variantsChromatin structureregulomeDiff Analysis tooldifferentially bound regionsdifferentially accessible regionsdifferentially methylated regionstranscriptional regulatory elementsepigenomic landscapesdata-mining suite
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#13 of 10,133
8818m citations

Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation

Shuai Wang et al.Journal of Clinical Investigation202410.1172/jci176851

Dimitris G. Placantonakis, Jeremy N. RichUniversity of Pittsburgh Medical Center, United States

glioblastomaGBM stem cellshistone lactylationlactateCBX3CD47phagocytosismicrogliamacrophagesEP300histone acetyltransferaselactyl-CoAanti-CD47 therapyimmunosuppressive cytokine profileMetabolic reprogrammingglycolysisImmune evasionepigenetic reprogrammingheterochromatintumor-associated macrophages
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#14 of 10,133
8118m citations

DPF2 reads histone lactylation to drive transcription and tumorigenesis

Guijin Zhai, Ziping Niu, Zixin Jiang et al.Proceedings of the National Academy of Sciences202410.1073/pnas.2421496121

Guijin Zhai, Ziping Niu, Zixin Jiang, Kai ZhangTianjin Medical University, China

lysine lactylationH3K14lahistone lactylationDPF2cervical cancerlactate accumulationMetabolic reprogrammingmultivalent photoaffinity probequantitative proteomicsEpigenetic readerCUT&Tagoncogenic gene transcriptionstructure-guided mutationDPF2-H3K14la interactiontranscriptional regulationcell survival
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#16 of 10,133
7518m citations

Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy

Tae Gun Kang et al.Science202410.1126/science.adl4492

Ben Youngblood, Caitlin C. ZebleySt. Jude Children's Research Hospital, United States

Clonal hematopoiesisT cell stemnessT cell exhaustionprogenitor-exhausted T cells (Tpex)Dnmt3aTet2Asxl1Immune checkpoint blockadeanti-PD-L1chronic antigen exposureH2AK119ubpolycomb group-repressive deubiquitinase pathwayT cell self-renewalCD8 T cell differentiationEpigenetic modificationAnti-tumor immunitytumor control
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#17 of 10,133
7418m citations

Systematic epigenome editing captures the context-dependent instructive function of chromatin modifications

Cristina Policarpi et al.Nature Genetics202410.1038/s41588-024-01706-w

Jamie A. HackettEuropean Molecular Biology Laboratory (EMBL), Italy

epigenome editingChromatin modificationH3K4me3H3K27me3H2AK119ubsingle-cell transcriptional readoutspromoter targetingChromatin remodelingDNA sequence motifscis-regulatory contextcombinatorial modificationssilencing penetrancemodular platformtranscriptional instructioncontext-dependent effectsswitch-like regulationattenuative regulationHistone modificationcausal perturbationtranscriptional heterogeneity
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#18 of 10,133
7418m citations

Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2‐Mediated MLH1 Intron Retention

Qu Yue et al.Advanced Science202410.1002/advs.202309290

Boyang Liu, Hongbo GuoSouthern Medical University, China

histone H3K9 lactylationtemozolomide resistanceglioblastomaLUC7L2MLH1 intron retentionmismatch repairCUT&TagSLAM-seqLDHA/Bstiripentolrecurrent glioblastomaPost-translational modificationalternative splicingepigenetic regulationmulti-omics analysisblood-brain barrier penetrationHistone lactylation inhibitioncombination therapy
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#19 of 10,133
7018m citations

Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA

Qing Dai, Chang Ye, Iryna Irkliyenko, Yiding Wang et al.Nature Biotechnology202410.1038/s41587-023-02034-w

Qing Dai, Chuan HeThe University of Chicago, United States

ultrafast bisulfite sequencingUBS-seq5-methylcytosine5mCm5CC-to-U conversioncfDNAmouse embryonic stem cellsm5C stoichiometryhighly structured RNA sequencesNSUN2HeLa mRNA5'-regions of mammalian mRNAmRNA translation regulationDNA damage reductionlow-input library construction
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#20 of 10,133
6818m citations

Mechanisms of action and resistance in histone methylation-targeted therapy

Makoto Yamagishi, Yuta Kuze et al.Nature202410.1038/s41586-024-07103-x

Makoto Yamagishi, Yutaka Suzuki, Kaoru UchimaruThe University of Tokyo, Japan

H3K27me3EZH1-EZH2 dual inhibitorvalemetostatadult T cell leukaemia/lymphomaChromatin condensationPRC2integrative single-cell analysesresistant clonesPRC2-compound interface mutationsTET2 mutationDNMT3A expressionde novo DNA methylationH3K27me3-associated regionsepigenetic resistance mechanismstumour suppressor gene reactivationprimary susceptibility subpopulationschromatin homeostasisEpigenetic inheritance
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Dominant research themes and year-over-year shifts in Epigenetics and DNA Methylation

What Topics Define the Class of 2026?

The Class of 2026 for Epigenetics and DNA Methylation is defined by a strong focus on DNA methylation and the emerging importance of metabolic interplay, highlighted by metabolic reprogramming and histone lactylation. Topics like epigenetic regulation and epigenetic clocks underscore the persistent interest in biological aging and fundamental regulatory mechanisms. This indicates a paradigm shift toward integrating epigenetics with metabolic states, particularly the role of metabolites like lactate in histone modifications.

Leading research themes
Leading research themes

How Did Topics Shift from the Class of 2025 to the Class of 2026?

The most dramatic shifts involve metabolism-linked epigenetics. Histone lactylation skyrocketed with a 7-fold increase, emerging as a major focus area alongside glycolysis and metabolic reprogramming, which saw a 2.3-fold increase. In contrast, traditional topics like histone modification and chromatin accessibility saw relative declines, suggesting a maturation of foundational profiling in favor of highly specific functional intersections, particularly those linking tumor metabolism and immune evasion with epigenetic reprogramming.

How topics shifted year over year
How topics shifted year over year
Methodology

PRI identifies high-impact research using a transparent, topic-agnostic framework applied consistently across scientific domains. Bibliographic records are drawn from OpenAlex, including publication dates, citation relationships, and document types.

This ranking covers the Class of 2026 cohort: journal articles published in 2024. Reviews and other non-article document types are excluded to ensure comparability.

Research impact is quantified with an 18-month post-publication citation window—the number of citing works published within 18 months of each paper's publication date. This metric captures early impact while controlling for publication age.

An LLM-based relevance classifier then reviews each candidate's title and abstract to confirm substantive alignment with the target domain. Only papers classified as relevant appear in the final ranking.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459

Full methodologyGitHubbioRxiv preprint

Cite this ranking

Pepkio Research Index (PRI). Topics and Trends in Most Cited Epigenetics and DNA Methylation Papers, Class of 2026. https://pri.pepkio.com/top-papers/epigenetics-and-dna-methylation/2026. Accessed 2026-07-19.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459