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State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs)
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State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs)

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 February 2026) | Viewed by 15208

Special Issue Editor

Dr. Xiaohong Zhang

E-Mail Website
Guest Editor
Hudson-Webber Cancer Research Center, Karmanos Cancer Institute, Detroit, MI 48201, USA
Interests: histone deacetylases (HDACs); DNA damage response; DNA repair; cell cycle checkpoint; E3 ligases; deubiquitinating enzymes (DUBs); lung cancer; chemoresistance; immunotherapy and cancer immunology

Special Issue Information

Dear Colleagues,

We are thrilled to present a Special Issue in Cells dedicated to the captivating realm of histone deacetylases and histone acetyltransferases.

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are two classes of enzymes catalyzing deacetylation and acetylation on lysine residues of core histones as well as non-histone proteins. HDACs include three Zn+-dependent HDAC families and an NAD+-dependent Sirtuin family. Recently, at least eight acylation modifications have been identified on lysine residues, such as crotonylation, malonylation, succinylation, glutarylation, etc. Interestingly, HDACs and HATs could serve as “erasers” and “writers” for some of these newly identified modifications. Therefore, HDACs and HATs may aptly be named lysine deacylases and lysine acyltransferases.

Both HDACs and HATs play important roles in almost all biological processes, such as gene expression, cell differentiation, apoptosis, metabolism, and immune responses. Both HDAC inhibitors and HAT inhibitors are used for the targeted therapy of tumors, inhibiting cell growth and promoting cell differentiation as well as apoptosis. The inhibition of HDACs or HATs has become an important approach to reverse the abnormal epigenetic and signaling changes associated with various cancers and non-cancer diseases.

We invite researchers, scholars, and experts from around the world to contribute their valuable insights to this Special Issue. By presenting your work on the role and involvement of HDACs and HATs in diseases, you have the opportunity to contribute to advancing our understanding of histone deacetylases and histone acetyltransferases.

We look forward to your contributions.

Dr. Xiaohong Zhang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • histone deacetylases
  • cancer
  • metabolism
  • immunotherapy
  • tumor microenvironment
  • DNA damage response
  • cell cycle

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Published Papers (5 papers)

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Review

21 pages, 527 KB  
Review
Current Understanding of SIRT7 Function and Its Emerging Roles in the Central Nervous System
by Yuchen Jiao, Chuangui Wang and Shengping Zhang
Cells 2026, 15(6), 548; https://doi.org/10.3390/cells15060548 - 19 Mar 2026
Viewed by 438
Abstract
SIRT7is an NAD+-dependent deacetylase predominantly localized in the nucleolus, where it plays important roles in chromatin regulation, transcriptional control, and cellular stress response. Accumulating evidence has revealed that SIRT7 participates in multiple molecular processes, including ribosomal RNA transcription, histone modification, DNA [...] Read more.
SIRT7is an NAD+-dependent deacetylase predominantly localized in the nucleolus, where it plays important roles in chromatin regulation, transcriptional control, and cellular stress response. Accumulating evidence has revealed that SIRT7 participates in multiple molecular processes, including ribosomal RNA transcription, histone modification, DNA damage repair, metabolic regulation, and inflammatory signaling pathways. Through these mechanisms, SIRT7 contributes to the pathogenesis of various human diseases, particularly cancer and metabolic disorders. In recent years, emerging studies have begun to uncover the roles of SIRT7 in the central nervous system (CNS). Although research in this area remains limited, available evidence suggests that SIRT7 may be involved in neuronal homeostasis, glial function, neuroinflammation, and responses to brain injury. Furthermore, dysregulation of SIRT7 has been implicated in CNS-related pathologies. In this review, we summarize the understanding of SIRT7 molecular mechanisms and its implications in human disease, with special emphasis on its emerging roles in the CNS. We also address unresolved questions and propose future research directions to facilitate a deeper understanding of SIRT7 in neurological physiology and pathology. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs))
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Figure 1

26 pages, 1102 KB  
Review
HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease
by Luan Pereira Diniz, Pedro de Sena Murteira Pinheiro, Lucas S. Franco and Flávia Carvalho Alcantara Gomes
Cells 2025, 14(17), 1338; https://doi.org/10.3390/cells14171338 - 29 Aug 2025
Cited by 7 | Viewed by 4155
Abstract
Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in [...] Read more.
Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cells, including astrocytes and microglia, HDACs orchestrate inflammatory responses, redox balance, and metabolic adaptations. We further examine the dysregulation of HDAC expression and activity in major neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Evidence from human post-mortem brain studies reveals region- and isoform-specific alterations in HDAC expression, which are closely associated with cognitive decline, mitochondrial dysfunction, and neuroinflammation. Preclinical studies support the use of HDAC inhibitors (HDACi) as neuroprotective agents, capable of restoring acetylation homeostasis, reducing neuroinflammation, and improving neuronal function. Given the relevance of HDACi, we summarize current clinical studies assessing the safety of these compounds in the context of tumor biology, as well as their potential future applications in neurodegenerative diseases. Together, this review underscores the dual significance of HDACs as biomarkers and therapeutic targets in the context of CNS disorders. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs))
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Figure 1

24 pages, 1719 KB  
Review
NAA10 (N-Alpha-Acetyltransferase 10): A Multifunctional Regulator in Development, Disease, and Cancer
by Zeng Quan Yang, Ion John Campeanu, Ivan Lopez, Manaal Syed, Yuanyuan Jiang and Hilda Afisllari
Cells 2025, 14(12), 863; https://doi.org/10.3390/cells14120863 - 7 Jun 2025
Cited by 1 | Viewed by 3034
Abstract
NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40–50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also [...] Read more.
NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40–50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also acetylates internal lysine residues of various proteins and exerts non-catalytic regulatory functions through diverse protein–protein interactions. Pathogenic variants in NAA10 are linked to a spectrum of developmental disorders, most notably Ogden syndrome, which is characterized by neurodevelopmental delay, cardiac defects, and craniofacial anomalies. In cancer, NAA10 is frequently overexpressed or genomically amplified, where its dysregulation correlates with tumor aggressiveness and poor prognosis. Functional studies implicate NAA10 in regulating cell cycle progression, apoptosis, migration, and other hallmarks of cancer. In this review, we summarize the structure, molecular mechanisms, and physiological functions of NAA10, as well as its roles in human diseases and cancer. We present in silico pan-cancer analyses that highlight its clinical significance and potential downstream pathways. Furthermore, we discuss the therapeutic potential and challenges of targeting NAA10 in cancer, and propose future research directions to better understand its multifaceted roles in health and disease. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs))
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Figure 1

20 pages, 1142 KB  
Review
Minichromosome Maintenance Proteins: From DNA Replication to the DNA Damage Response
by Agnes Malysa, Xiaohong Mary Zhang and Gerold Bepler
Cells 2025, 14(1), 12; https://doi.org/10.3390/cells14010012 - 26 Dec 2024
Cited by 6 | Viewed by 3218
Abstract
The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to [...] Read more.
The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system. Dysfunctional DNA replication and DDR are a source of genomic instability, causing heritable mutations that drive cancer evolutions. The family of minichromosome maintenance (MCM) proteins plays an important role not only in DNA replication but also in DDR. Here, we will review the current strides of MCM proteins in these integrated processes as well as the acetylation/deacetylation of MCM proteins and the value of MCMs as biomarkers in cancer. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs))
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Figure 1

19 pages, 952 KB  
Review
The Structures, Functions, and Roles of Class III HDACs (Sirtuins) in Neuropsychiatric Diseases
by Robin E. Bonomi, William Riordan and Juri G. Gelovani
Cells 2024, 13(19), 1644; https://doi.org/10.3390/cells13191644 - 2 Oct 2024
Cited by 3 | Viewed by 3270
Abstract
Over the past two decades, epigenetic regulation has become a rapidly growing and influential field in biology and medicine. One key mechanism involves the acetylation and deacetylation of lysine residues on histone core proteins and other critical proteins that regulate gene expression and [...] Read more.
Over the past two decades, epigenetic regulation has become a rapidly growing and influential field in biology and medicine. One key mechanism involves the acetylation and deacetylation of lysine residues on histone core proteins and other critical proteins that regulate gene expression and cellular signaling. Although histone deacetylases (HDACs) have received significant attention, the roles of individual HDAC isoforms in the pathogenesis of psychiatric diseases still require further research. This is particularly true with regard to the sirtuins, class III HDACs. Sirtuins have unique functional activity and significant roles in normal neurophysiology, as well as in the mechanisms of addiction, mood disorders, and other neuropsychiatric abnormalities. This review aims to elucidate the differences in catalytic structure and function of the seven sirtuins as they relate to psychiatry. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Histone Deacetylases (HDACs) and Histone Acetyltransferases (HATs))
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