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The Role of Histone Modifications, Variants and Mutations in Gene Regulation and Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 14724

Special Issue Editor

Dr. Kui Ming Chan

E-Mail Website
Guest Editor
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
Interests: epigenetics; chromatin biology; cancer epigenetics; X-chromosome inactivation; histone mutation; oncohistones
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Histones are small nuclear proteins that are required for packaging genomic DNA into the nucleus. Importantly, histones also serve as epigenetic elements for gene regulation without changing the DNA sequence. Over the past two decades, dozens of histone modifications and a variety of histone variants have been identified; however, the molecular mechanisms by which each (and the combinations) of these epigenetic factors are not yet fully understood. In contrast to regulating gene expression under physiological conditions, “mutant” histones have been implicated in human diseases through distinct mechanisms. Recent studies of the K-to-M oncohistones of histone H3 and the other missense histone mutations in H2B and H4 demonstrated that histones play a significant role in maintenance of the genome’s stability. 

This Special Issue “The role of histone modifications, variants and mutations in gene regulation and human diseases” aims to provide new insight into the gene regulation functions of different histone modifications and variants in gene regulation and the mechanisms of different oncohistones in human diseases. Authors are invited to submit original research and review articles related to these subjects.

Dr. Kui Ming Chan
Guest Editor

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Keywords

  • epigenetics
  • chromatin biology
  • cancer epigenetics
  • X-chromosome inactivation
  • histone mutation
  • oncohistones

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Published Papers (3 papers)

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Review

37 pages, 3645 KiB  
Review
Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment
by Po Man Lai and Kui Ming Chan
Int. J. Mol. Sci. 2024, 25(6), 3144; https://doi.org/10.3390/ijms25063144 - 9 Mar 2024
Cited by 4 | Viewed by 2770
Abstract
Histones are nuclear proteins essential for packaging genomic DNA and epigenetic gene regulation. Paralogs that can substitute core histones (H2A, H2B, H3, and H4), named histone variants, are constitutively expressed in a replication-independent manner throughout the cell cycle. With specific chaperones, they can [...] Read more.
Histones are nuclear proteins essential for packaging genomic DNA and epigenetic gene regulation. Paralogs that can substitute core histones (H2A, H2B, H3, and H4), named histone variants, are constitutively expressed in a replication-independent manner throughout the cell cycle. With specific chaperones, they can be incorporated to chromatin to modify nucleosome stability by modulating interactions with nucleosomal DNA. This allows the regulation of essential fundamental cellular processes for instance, DNA damage repair, chromosomal segregation, and transcriptional regulation. Among all the histone families, histone H2A family has the largest number of histone variants reported to date. Each H2A variant has multiple functions apart from their primary role and some, even be further specialized to perform additional tasks in distinct lineages, such as testis specific shortH2A (sH2A). In the past decades, the discoveries of genetic alterations and mutations in genes encoding H2A variants in cancer had revealed variants’ potentiality in driving carcinogenesis. In addition, there is growing evidence that H2A variants may act as novel prognostic indicators or biomarkers for both early cancer detection and therapeutic treatments. Nevertheless, no studies have ever concluded all identified variants in a single report. Here, in this review, we summarize the respective functions for all the 19 mammalian H2A variants and their roles in cancer biology whilst potentiality being used in clinical setting. Full article
(This article belongs to the Special Issue The Role of Histone Modifications, Variants and Mutations in Gene Regulation and Human Diseases)
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21 pages, 21855 KiB  
Review
The Role of Histone Modification in DNA Replication-Coupled Nucleosome Assembly and Cancer
by Yaguang Zhang, Qin Zhang, Yang Zhang and Junhong Han
Int. J. Mol. Sci. 2023, 24(5), 4939; https://doi.org/10.3390/ijms24054939 - 3 Mar 2023
Cited by 9 | Viewed by 6059
Abstract
Histone modification regulates replication-coupled nucleosome assembly, DNA damage repair, and gene transcription. Changes or mutations in factors involved in nucleosome assembly are closely related to the development and pathogenesis of cancer and other human diseases and are essential for maintaining genomic stability and [...] Read more.
Histone modification regulates replication-coupled nucleosome assembly, DNA damage repair, and gene transcription. Changes or mutations in factors involved in nucleosome assembly are closely related to the development and pathogenesis of cancer and other human diseases and are essential for maintaining genomic stability and epigenetic information transmission. In this review, we discuss the role of different types of histone posttranslational modifications in DNA replication-coupled nucleosome assembly and disease. In recent years, histone modification has been found to affect the deposition of newly synthesized histones and the repair of DNA damage, further affecting the assembly process of DNA replication-coupled nucleosomes. We summarize the role of histone modification in the nucleosome assembly process. At the same time, we review the mechanism of histone modification in cancer development and briefly describe the application of histone modification small molecule inhibitors in cancer therapy. Full article
(This article belongs to the Special Issue The Role of Histone Modifications, Variants and Mutations in Gene Regulation and Human Diseases)
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19 pages, 1823 KiB  
Review
The Roles of Histone Post-Translational Modifications in the Formation and Function of a Mitotic Chromosome
by Marco A. Andonegui-Elguera, Rodrigo E. Cáceres-Gutiérrez, Alejandro López-Saavedra, Fernanda Cisneros-Soberanis, Montserrat Justo-Garrido, José Díaz-Chávez and Luis A. Herrera
Int. J. Mol. Sci. 2022, 23(15), 8704; https://doi.org/10.3390/ijms23158704 - 5 Aug 2022
Cited by 7 | Viewed by 4425
Abstract
During mitosis, many cellular structures are organized to segregate the replicated genome to the daughter cells. Chromatin is condensed to shape a mitotic chromosome. A multiprotein complex known as kinetochore is organized on a specific region of each chromosome, the centromere, which is [...] Read more.
During mitosis, many cellular structures are organized to segregate the replicated genome to the daughter cells. Chromatin is condensed to shape a mitotic chromosome. A multiprotein complex known as kinetochore is organized on a specific region of each chromosome, the centromere, which is defined by the presence of a histone H3 variant called CENP-A. The cytoskeleton is re-arranged to give rise to the mitotic spindle that binds to kinetochores and leads to the movement of chromosomes. How chromatin regulates different activities during mitosis is not well known. The role of histone post-translational modifications (HPTMs) in mitosis has been recently revealed. Specific HPTMs participate in local compaction during chromosome condensation. On the other hand, HPTMs are involved in CENP-A incorporation in the centromere region, an essential activity to maintain centromere identity. HPTMs also participate in the formation of regulatory protein complexes, such as the chromosomal passenger complex (CPC) and the spindle assembly checkpoint (SAC). Finally, we discuss how HPTMs can be modified by environmental factors and the possible consequences on chromosome segregation and genome stability. Full article
(This article belongs to the Special Issue The Role of Histone Modifications, Variants and Mutations in Gene Regulation and Human Diseases)
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