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MiR-29 represses the activities of DNA methyltransferases and DNA demethylases.

ABSTRACT: Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA.

SUBMITTER: Morita S

PROVIDER: S-EPMC3742264 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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miR-29 represses the activities of DNA methyltransferases and DNA demethylases.

Morita Sumiyo S Horii Takuro T Kimura Mika M Ochiya Takahiro T Tajima Shoji S Hatada Izuho I

International journal of molecular sciences 20130712 7

Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposi ...[more]

PMID: 23857059

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Project description:Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.

Project description:Potato is a temperate crop consumed globally as a staple food. High temperature negatively impacts the tuberization process, eventually affecting crop yield. DNA methylation plays an important role in various developmental and physiological processes in plants. It is a conserved epigenetic mark determined by the dynamic concurrent action of cytosine-5 DNA methyltransferases (C5-MTases) and demethylases (DeMets). However, C5-MTases and DeMets remain unidentified in potato, and their expression patterns are unknown under high temperatures. Here, we performed genome-wide analysis and identified 10 C5-MTases and 8 DeMets in potatoes. Analysis of their conserved motifs, gene structures, and phylogenetic analysis grouped C5-MTases into four subfamilies (StMET, StCMT3, StDRM, and StDNMT2) and DeMets into three subfamilies (StROS, StDML, and StDME). Promoter analysis showed the presence of multiple cis-regulatory elements involved in plant development, hormone, and stress response. Furthermore, expression dynamics of C5-MTases and DeMets were determined in the different tissues (leaf, flower, and stolon) of heat-sensitive (HS) and heat-tolerant (HT) genotypes under high temperature. qPCR results revealed that high temperature resulted in pronounced upregulation of CMT and DRM genes in the HT genotype. Likewise, demethylases showed strong upregulation in HT genotype as compared to HS genotype. Several positive (StSP6A and StBEL5) and negative (StSP5G, StSUT4, and StRAP1) regulators are involved in the potato tuberization. Expression analysis of these genes revealed that high temperature induces the expression of positive regulators in the leaf and stolon samples of HT genotype, possibly through active DNA demethylation and RNA-directed DNA methylation (RdDM) pathway components. Our findings lay a framework for understanding how epigenetic pathways synergistically or antagonistically regulate the tuberization process under high-temperature stress in potatoes. Uncovering such mechanisms will contribute to potato breeding for developing thermotolerant potato varieties.

Dataset Information

MiR-29 represses the activities of DNA methyltransferases and DNA demethylases.

Publications

miR-29 represses the activities of DNA methyltransferases and DNA demethylases.

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