The disorders of DNA and histone methylation have a close relationship with the development and progression of tumors. Epigenetic regulation is critical in maintaining the stability and integrity of the expression profiles of different cell types by modifying DNA methylation and histone methylation. However, the abnormal changes of methylation often result in the development and progression of tumors. This review summarized the theory of tumor genomic and histone methylation, detection methods of methylation and their applications, and the clinical application of methylation as biological markers and drug targets.
DNA Methylation ; Histones ; metabolism ; Humans ; Methylation ; Neoplasms ; genetics ; metabolism

Lysine acetylation is one of the major post-translational modifications and plays critical roles in regulating gene expression and protein function. Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from the lysines of both histone and non-histone proteins. The RPD3 family is the most widely studied HDACs. This article summarizes the regulatory mechanisms of Arabidopsis RPD3 family in several growth and development processes, which provide a reference for studying the mechanisms of RPD3 family members in regulating plant development. Moreover, this review may provide ideas and clues for exploring the functions of other members of HDACs family.
Arabidopsis/metabolism* ; Histone Deacetylases/metabolism* ; Histones ; Plant Development/genetics*

Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.
Acetylation ; Carcinogenesis ; Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Methylation ; Phosphorylation

Many pathological phenomena of male infertility are related to epigenetic changes in male germ cells. Epigenetic regulation during spermatogenesis plays an important role in mitotic/meiotic divisions and spermiogenesis. The histones have various post-translational modifications on different amino acid residues during spermatogenesis. These modifications are crucial to the precise regulation of spermatogenesis. Moreover, the histone-to-protamine transition will occur during spermiogenesis. Many studies have also found that abnormal changes of histone modifications during spermatogenesis may damage the sperm development, leading to male sterility. This article reviews the changes of histone modifications during spermatogenesis, the regulation of the development of male germ cells, and the relationship between histone abnormalities and male sterility.
Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Infertility, Male ; physiopathology ; Male ; Spermatogenesis

As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.
Animals ; Histones ; Humans ; Lysine ; Neoplasms ; Signal Transduction ; Sirtuins ; metabolism

Cancer stem cells (CSCs), a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA (ncRNA) including microRNAs and long non-coding RNAs (lncRNAs), and histone-modifiers, such as let-7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, lncRNAs and histone-modifiers especially Polycomb family proteins in regulating breast cancer stem cells (BCSCs).
Breast Neoplasms ; genetics ; metabolism ; pathology ; Histones ; metabolism ; Humans ; Neoplastic Stem Cells ; metabolism ; RNA, Untranslated ; genetics ; metabolism

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
Humans ; Transcription Factors/metabolism* ; Nuclear Proteins/metabolism* ; Histones ; Cell Cycle Proteins/metabolism* ; Neoplasms/metabolism* ; Protein Domains

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.
Nucleosomes ; Histones/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Lysine/metabolism* ; Methyltransferases/metabolism* ; Methylation

Inflammatory bowel disease refers to chronic inflammatory disorders that affect the gastrointestinal tract. Ubiquitination is an important protein post-translational modification. In recent years, the research of ubiquitination-deubiquitination system in the development of inflammatory bowel disease has become a hot spot. Up to now, the E3 ubiquitin ligases such as ring finger protein 183 (RNF183), RNF20, Itch and A20 were well studied in inflammatory bowel disease. RNF183 promotes the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα; RNF20 drives histone H2B monoubiquitylation, downregulates a panel of inflammation-associated genes; Itch inhibits IL-17-mediated colon inflammation by retinoid acid related orphan receptor γt ubiquitination; A20 has ubiquitinating-deubiquitinating activity to regulates colon inflammation. This article reviews the role and regulatory mechanism of RNF183, RNF20, Itch and A20 in the pathogenesis of inflammatory bowel disease.
Histones ; metabolism ; Humans ; Inflammatory Bowel Diseases ; physiopathology ; NF-kappa B ; metabolism ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*