Human dental pulp stem cells (DPSCs) have emerged as an important source of stem cells in the tissue engineering, and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration. Nevertheless, little is known about the complicated molecular mechanisms. In this study, we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition. Hypoxia was induced in DPSCs by Cobalt chloride (CoCl
Cell Differentiation ; Histone-Lysine N-Methyltransferase ; Humans ; Hypoxia ; Methyltransferases ; MicroRNAs

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*

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

As a crucial part of epigenetic regulation, the histone modification catalyzed by histone modification enzymes can alter the chromatin structure and modulate the gene expression. The role of histone modification in disease pathogenesis, especially in tumorigenesis, has become a research hotspot. The deregulation of histone modification, such as the overexpression and gain-of-function mutations of histone methyltransferase EZH2, the inactive mutations of histone methyltransferase MLL2, histone acetyltransferase CREBBP and EP300 are crucial for the development of hematological neoplasms. Some of Epi-drugs such as HDAC inhibitors, EZH2 inhibitors, are already clinically used, some are still in basic research stage, which are important field of new drug development for hematological neoplasms. In this review, the researches advances of basic medical sciences and clinical applications of aberrant histone modifications in hematological neoplasms are summarized.
Cell Transformation, Neoplastic ; Epigenesis, Genetic ; Hematologic Neoplasms ; Histone Deacetylase Inhibitors ; Histone-Lysine N-Methyltransferase ; Histones ; Humans

Histone methylation is one of the most widely studied post-transcriptional modifications. It is thought to be an important epigenetic event that is closely associated with cell fate determination and differentiation. To explore the spatiotemporal expression of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) epigenetic marks and methylation or demethylation transferases in tooth organ development, we measured the expression of SET7, EZH2, KDM5B and JMJD3 via immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis in the first molar of BALB/c mice embryos at E13.5, E15.5, E17.5, P0 and P3, respectively. We also measured the expression of H3K4me3 and H3K27me3 with immunofluorescence staining. During murine tooth germ development, methylation or demethylation transferases were expressed in a spatial-temporal manner. The bivalent modification characterized by H3K4me3 and H3K27me3 can be found during the tooth germ development, as shown by immunofluorescence. The expression of SET7, EZH2 as methylation transferases and KDM5B and JMJD3 as demethylation transferases indicated accordingly with the expression of H3K4me3 and H3K27me3 respectively to some extent. The bivalent histone may play a critical role in tooth organ development via the regulation of cell differentiation.
Animals ; Cell Differentiation ; physiology ; DNA-Binding Proteins ; analysis ; Dental Papilla ; embryology ; Embryo, Mammalian ; Enamel Organ ; embryology ; Enhancer of Zeste Homolog 2 Protein ; Epigenesis, Genetic ; physiology ; Gene Expression Regulation, Developmental ; Histone-Lysine N-Methyltransferase ; analysis ; Histones ; metabolism ; Jumonji Domain-Containing Histone Demethylases ; analysis ; Lysine ; metabolism ; Methylation ; Mice ; Mice, Inbred BALB C ; Odontogenesis ; physiology ; Polycomb Repressive Complex 2 ; analysis ; Protein Processing, Post-Translational ; physiology ; Tooth Germ ; embryology

Twenty-three histone methyltransferase genes were obtained from transcriptome dataset of Lonicera japonica. The nucleotide and proteins characteristics, subcellular localization, senior structural domains and conservative forecasting were analyzed. The result of phylogenetic tree showed that 23 histone methyltransferases were mainly divided into two groups: lysine methyltransferase and arginine methyltransferases. The result of gene expression showed that 23 histone methyltransferases showed preference in terms of interspecies and organs. They were more expressed in buds of L. japonica than in L. japonica var. chinensis and lower in leaves of L. japonica than in L. japonica var. chinensis. Eight genes were specific expressed in flower. These results provided basis for further understanding the function of histone methyltransferase and epigenetic regulation of active ingredients of L. japonica.
Computational Biology ; Gene Expression ; Histone-Lysine N-Methyltransferase ; genetics ; Lonicera ; enzymology ; genetics ; Phylogeny

Hematopoietic Stem Cells ; Histone-Lysine N-Methyltransferase ; Histones ; Humans ; Leukemia ; pathology

Mixed linked leukemia 4 (MLL4) is a specific methyltransferase of histone 3 position lysine 4 (H3K4). It is also one of the important members of COMPASS/Set1-like protein complex. Both MLL4 protein itself and its mediated H3K4 methylation modification can cause changes in chromatin structure and function, thus regulating gene transcription and expression. With the studies of MLL4 protein in recent years, the roles of MLL4 gene, MLL4 protein and protein complex in the development of tissues and organs, tumor diseases and other physiological and pathophysiological processes have been gradually revealed. In this paper, the research progress of MLL4 gene, MLL4 protein characteristics, biological function and its effect on disease were reviewed, in order to further understand the effect of histone methyltransferase on gene expression regulation, as well as its non-enzyme dependent function. This paper may provide new ideas for the prevention, diagnosis and treatment of related diseases.
DNA-Binding Proteins ; physiology ; Histone-Lysine N-Methyltransferase ; physiology ; Histones ; chemistry ; Humans ; Methylation

Histone lysine methyltransferase EZH2 has been reported to be frequently overexpressed in hepatocellular carcinoma (HCC) tissues and associated with hepatocarcinogenesis. However, the exact mechanism of EZH2 up-regulation in HCC has not been determined. In this study, we used murine hepatocyte AML12 cells to investigate the role of hepatitis B virus X protein (HBx) in regulating the expression of mEZH2. Western blot analysis demonstrated that the expression level of mEZH2 protein in AML12 cells was up-regulated by HBx in a dose-dependent manner. To further investigate the mechanism of mEZH2 overexpression, the 2500 bp regulatory sequence upstream from the first exon of the mEZH2 gene was amplified from AML12 genomic DNA and constructed into a luciferase reporter plasmid. The luciferase activity of the mEZH2 promoter significantly increased in AML12 cells co-transfected with HBx plasmid, and deleting the -486/-214 promoter region decreased HBx-induced mEZH2 promoter activation by nearly 50%. The -486/-214 region was then analyzed in the TRANSFAC 6.0 database and a typical E2F1-binding site was found. Mutation of this E2F1-binding site or knockdown of E2F1 expression by RNAi led to a dramatic decrease in HBx-induced activation of the mEZH2 promoter and mEZH2 overexpression in AML12 cells. These results provide evidence that HBx up-regulates mEZH2 expression by transactivating the mEZH2 promoter through E2F1 transcription factor, thereby providing new epigenetic evidence for the carcinogenic effect of HBx.
Animals ; Binding Sites ; Cell Line ; E2F1 Transcription Factor ; genetics ; Enhancer of Zeste Homolog 2 Protein ; Hepatocytes ; cytology ; metabolism ; virology ; Histone-Lysine N-Methyltransferase ; genetics ; metabolism ; Mice ; Plasmids ; Polycomb Repressive Complex 2 ; Promoter Regions, Genetic ; genetics ; RNA, Small Interfering ; genetics ; Trans-Activators ; genetics ; metabolism ; Transfection ; Up-Regulation

OBJECTIVETo study the role of Ezh2 in the all-trans retinoic acid RA induced P19 neural differentiation.

METHODSThe expression of Ngn1 in the RA induced P19 cells was detected at the mRNA and protein levels using real time RT-PCR and Western blot assays. The binding of Ezh2 and H3K27me3 on the Ngn 1 promoter was analyzed using chromatin immunoprecipitation assay.

RESULTIn the RA induced P19 cells, the recruitment of Ezh2 and its methylated substrate H3K27me3 on the promoter of Ngn 1 gene elevated in the first 2 days, and then declined rapidly, followed by the initiation of neuronal differentiation.

CONCLUSIONSEzh2 produces a repressive histone mark H3K27me3 in the early stage of RA induced P12 cells. By avoiding the premature expression of Ngn1 gene, Ezh2 can ensure the normal differentiation of P19 cells.

Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Cell Differentiation ; drug effects ; physiology ; Enhancer of Zeste Homolog 2 Protein ; Histone-Lysine N-Methyltransferase ; genetics ; metabolism ; Histones ; metabolism ; Mice ; Nerve Tissue Proteins ; genetics ; metabolism ; Neurons ; cytology ; drug effects ; metabolism ; Polycomb Repressive Complex 2 ; Tretinoin ; pharmacology ; Tumor Cells, Cultured