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Animals : an open access journal from MDPI2026; 16(6); 891; doi: 10.3390/ani16060891

H3K4me3 CUT&Tag and Transcriptome Analysis Reveal the Epigenetic Regulatory Landscape in Mammary Gland Tissues of Yili Horses at Different Lactation Stages.

Abstract: H3K4me3, a well-established histone modification associated with active promoters, plays a critical role in orchestrating gene expression programs that govern mammary gland development and lactation. In this study, we present the first comprehensive epigenomic profiling of H3K4me3 modifications during mammary gland development in Yili horses using Cleavage Under Targets and Tagmentation (CUT&Tag) and RNA sequencing. Mammary gland tissues were collected from two developmental stages-early lactation and peak lactation. A total of 393 differentially expressed genes (DEGs) were identified between two groups, among which 72 DEGs (54 upregulated H3K4me3 targets and 18 downregulated targets) were directly regulated by H3K4me3. KEGG enrichment analyses revealed that these DEGs were involved in ECM-receptor interaction, focal adhesion, the PI3K-Akt signaling pathway, and the calcium signaling pathway. In these pathways, five genes were identified as potential regulators of mammary gland development. Among these, PTGES, COL1A1, PDGFRB, and RYR1 exhibited consistent upregulation at both the transcriptomic and chromatin levels, whereas PRKAG3 showed significant downregulation. These findings offer novel insights into the epigenetic regulation of lactation in horses and lay a theoretical foundation for improving milk production traits through targeted molecular breeding strategies.
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Publication Date: 2026-03-12 PubMed ID: 41897868PubMed Central: PMC13023263DOI: 10.3390/ani16060891Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates how the histone modification H3K4me3 influences gene expression during different stages of lactation in the mammary glands of Yili horses.
  • Using advanced genomic techniques, researchers identified key genes and pathways regulated epigenetically that are important for mammary gland development and lactation.

Introduction to the Research

  • H3K4me3 role: H3K4me3 is a histone modification known to mark active gene promoters and plays a crucial role in controlling gene expression.
  • Mammary gland function: Development and lactation in mammary glands require tightly controlled gene expression programs, influenced by epigenetic factors like H3K4me3.
  • Objective: To profile H3K4me3 modification patterns in the mammary glands of Yili horses and link these epigenetic marks to gene expression changes across lactation stages.

Methodology

  • Sample collection: Mammary gland tissues were obtained from Yili horses at two time points: early lactation and peak lactation.
  • Epigenomic profiling: Cleavage Under Targets and Tagmentation (CUT&Tag) was used to map the genome-wide distribution of the H3K4me3 histone mark in the collected tissues.
  • Transcriptome analysis: RNA sequencing was performed on the same samples to measure gene expression levels.
  • Integration of data: Researchers correlated changes in H3K4me3 occupancy with differential gene expression to identify genes directly regulated by this histone modification.

Key Findings

  • Differentially expressed genes (DEGs): A total of 393 genes showed differing expression between early and peak lactation stages.
  • Direct H3K4me3 regulation: Among those, 72 DEGs were identified as direct targets of H3K4me3 modification — 54 had increased H3K4me3 and expression, 18 showed decreases.
  • Enriched biological pathways: KEGG pathway analysis indicated that these genes are involved in critical pathways such as:
    • ECM-receptor interaction (extracellular matrix signaling)
    • Focal adhesion (cell attachment and signaling)
    • PI3K-Akt signaling pathway (cell growth and survival)
    • Calcium signaling pathway (important for cellular function and signaling)
  • Potential key regulatory genes: Five genes (PTGES, COL1A1, PDGFRB, RYR1, and PRKAG3) were highlighted as likely major regulators of mammary gland development due to their consistent epigenetic and transcriptional changes.
    • PTGES, COL1A1, PDGFRB, and RYR1 were upregulated in both transcriptome and H3K4me3 signals.
    • PRKAG3 showed significant downregulation across both measures.

Significance and Implications

  • This study provides the first epigenomic map of H3K4me3 in horse mammary tissue during lactation, revealing how epigenetic modifications regulate gene expression during this process.
  • The identified regulatory genes and pathways deepen understanding of the molecular control of lactation in horses.
  • Findings offer new targets for molecular breeding, with potential to improve milk production and quality in Yili horses.
  • The integrated approach combining CUT&Tag with transcriptomics exemplifies how epigenetics can be harnessed to enhance livestock traits.

Cite This Article

APA
Liu L, Cao H, Ma H, Chen B, Liu W. (2026). H3K4me3 CUT&Tag and Transcriptome Analysis Reveal the Epigenetic Regulatory Landscape in Mammary Gland Tissues of Yili Horses at Different Lactation Stages. Animals (Basel), 16(6), 891. https://doi.org/10.3390/ani16060891

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 16
Issue: 6
PII: 891

Researcher Affiliations

Liu, Lingling
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
Cao, Hang
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
Ma, Haiyu
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
Chen, Bin
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
Liu, Wujun
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.

Grant Funding

  • 2023TSYCCX0033 / the Tianshan Talent Cultivation Program of the Xinjiang Uygur Autonomous Region

Conflict of Interest Statement

The authors declare no conflicts of interest.

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