Decoding the Epigenetic Language: Combinatorial Chromatin Modifications in Gene Regulation

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Epigenomics".

Deadline for manuscript submissions: closed (20 December 2025) | Viewed by 167

Special Issue Editors


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Guest Editor
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: gene regulation; epigenetics; biophysics and structural biology

E-Mail Website
Guest Editor
The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: gene regulation; epigenetics; biophysics and structural biology

Special Issue Information

Dear Colleagues,

Epigenetic regulation, through dynamic and reversible chromatin modifications, plays a fundamental role in controlling gene expression across diverse biological contexts. Recent advances have highlighted the combinatorial nature of these chromatin marks—so-called "epigenetic language"—as crucial in decoding the regulatory complexity of the genome.

This Special Issue, “Decoding the Epigenetic Language: Combinatorial Chromatin Modifications in Gene Regulation”, will explore how combinations of DNA methylation, histone modifications, non-coding RNAs, and chromatin remodelers influence transcriptional regulation, genome stability, and disease etiology. We also aim to emphasize the interplay between these marks, and a particular emphasis will be placed on their roles in cancer epigenetics, developmental processes, and host–pathogen interactions, as well as their implications in precision medicine.

Over the last two decades, the field has evolved from identifying individual epigenetic marks to understanding their integration and crosstalk in chromatin landscapes. This evolution has been driven by powerful tools such as ChIP-seq, CUT&RUN, ATAC-seq, and integrative multi-omics, along with advances in structural biology and AI-driven analysis.

We welcome submissions of cutting-edge research that delves into the mechanisms behind combinatorial chromatin regulation, its functional implications in health and disease, and advances in methodology that can drive the field forward. Original research articles and comprehensive reviews that uncover mechanistic insights, utilize innovative model systems, or develop computational and AI-based tools to decode chromatin modification patterns will be considered. Studies addressing epigenetic dysregulation in disease models, the therapeutic targeting of chromatin regulators, or novel methodological frameworks are particularly welcome.

Through this Special Issue, we hope to develop a deeper understanding of chromatin-based regulation and foster interdisciplinary dialog in this rapidly evolving field.

We look forward to receiving your valuable contributions to this timely and important Special Issue.

Dr. Kaur Gundeep
Dr. John R. Horton
Guest Editors

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Keywords

  • epigenetics
  • gene regulation
  • chromatin modifications
  • chromatin architecture
  • computational epigenomics
  • CRISPR epigenome editing
  • epigenetic therapies

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Published Papers (1 paper)

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Review

16 pages, 320 KB  
Review
HNF4α as a Master Regulator of Epigenetic Dynamics in Epithelial Cells
by Laura Amicone, Carla Cicchini and Alessandra Marchetti
Genes 2026, 17(1), 41; https://doi.org/10.3390/genes17010041 - 31 Dec 2025
Abstract
Hepatocyte nuclear factor 4 α (HNF4α) is a master transcriptional regulator essential for the maintenance of epithelial cell identity and function. Beyond its well-established role in controlling metabolic and differentiation programs, recent evidence highlights HNF4α as a key determinant of epithelial epigenetic reprogramming. [...] Read more.
Hepatocyte nuclear factor 4 α (HNF4α) is a master transcriptional regulator essential for the maintenance of epithelial cell identity and function. Beyond its well-established role in controlling metabolic and differentiation programs, recent evidence highlights HNF4α as a key determinant of epithelial epigenetic reprogramming. Through direct interaction with chromatin modifiers and pioneer factors, HNF4α contributes to the establishment, maintenance, and dynamically reshaping of epithelial-specific transcriptional programs at epigenetic level. In this review, we summarize current knowledge on how HNF4α shapes chromatin organization by recruiting chromatin modifiers, modulating nucleosome positioning and regulating chromatin loop formation, thus directing tissue-specific gene expression. We also examine its direct regulation of epigenetic modifiers, as well as of epi-miRNAs and epi-lncRNAs, underscoring its role in coordinating chromatin remodeling with transcriptional networks. Finally, we address how dynamic HNF4α occupancy and activity influence context-dependent transcriptional outputs, and how disease-related alterations of its expression and function can contribute to epithelial dysfunction. Understanding the epigenetic functions of HNF4α provides new insights into epithelial biology and reveals potential therapeutic opportunities for restoring epithelial homeostasis in disease contexts. Full article
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