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*

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

Chromosomal Proteins, Non-Histone ; chemistry ; genetics ; metabolism ; HeLa Cells ; Histones ; chemistry ; genetics ; metabolism ; Humans ; Protein Domains

Epigenetic modifications, including DNA methylation, histone modifications, RNA epigenetics and nucleosome remodeling, are important for gene transcription, but such modifications do not change the coding sequence of the gene. Although these events are heritable, they are potentially reversible, thus opening up opportunities for the therapy of cancer. So epigenetic modifications have been thrusted into the forefront of new drug discoveries. Current knowledge suggests that the agents that intervene epigenetics by "turning back on" silenced genes may represent a significant advancement in treating many forms of cancer. In this review, we summarized the research progress of epigenetic gene regulation and the proteins which could read epigenetic codes. And the relationship between epigenetics and cancer was discussed comprehensively.
DNA Methylation ; Epigenesis, Genetic ; genetics ; Gene Expression Regulation ; genetics ; Histones ; metabolism ; Humans ; Neoplasms ; genetics ; therapy

The occurence and development of tumors is a complicated process, which not only depends on the mutation or deletion of genes, but also is affected by epigenetic regulation. Accumulating evidences have shown that epigenetic modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation, DNA damage response and tumor development. SET domain containing lysine methyltransferase 7 (SETD7) was initially identified as an important lysine methyltransferase, which methylated histone and non-histone proteins. These modifications play fundamental roles. Once this modification disorders, it can directly lead to cell abnormalities and cause many diseases. Studies have shown that SETD7 is related to the occurence and development of various tumors, but the methylation sites of SETD7 and its regulatory mechanism have not been fully elucidated. This article summarizes the research progress of the role of SETD7 on histone and non-histone methylation modification in tumors and the molecular mechanism, in order to provide new therapeutic targets for tumor pathogenesis and diagnosis.
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Humans ; Epigenesis, Genetic ; Histone-Lysine N-Methyltransferase/metabolism* ; Lysine/metabolism* ; Lung Neoplasms/genetics* ; Histones/metabolism*

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*

Chromatin ; genetics ; metabolism ; Epigenesis, Genetic ; Genomic Instability ; Histones ; metabolism ; Humans ; Neoplasms ; metabolism ; pathology ; Ubiquitin-Protein Ligases ; genetics ; metabolism

In recent years, the role of epigenetic modifications in tumorigenesis drawn more and more attention. The aberrant changes of histone modifications have been found in leukemias, whereby loss of balance in H3K9 methylation is associated closely with leukemogenesis. SUV39H1, the first described histone H3 lysine 9 methyltransferase takes part in heterochromatin formation and gene transcription regulation. It could be a new target for leukemia therapy by correcting the aberrance of H3K9 methylation, inducing the reexpression of tumor suppressor genes. This review discusses how H3K9 methylation regulating gene transcription, silencing gene expression and its association with leukemia.
Animals ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Histones ; genetics ; metabolism ; Humans ; Leukemia ; genetics ; metabolism ; Lysine ; metabolism ; Methylation

Epigenetic abnormalities not only associated with carcinogenesis, they may also influence the curative effect and prognosis of anticancer drugs through modifying pharmacokinetic genes related to drug absorption, distribution, metabolism, excretion and pharmacodynamic genes related to signaling pathways and targets. That drugs through regulating epigenetic factors pocessing anti-cancer effect is becoming a research hot spot. We summarized and analyzed the realtionship of DNA methylation, miRNA, and histone modification with antitumor drug effect, aiming at promoting rational use of antitumor drugs and providing new ideas on developing epi-drugs.
Antineoplastic Agents ; therapeutic use ; DNA Methylation ; Epigenesis, Genetic ; Histones ; genetics ; metabolism ; Humans ; MicroRNAs ; metabolism ; Neoplasms ; drug therapy ; genetics