BackgroundDNA hypermethylation at promoter CpG islands (CGIs) is a hallmark of cancers and could lead to dysregulation of gene expression in the development of cancers, however, its dynamics and regulatory mechanisms remain elusive. Bivalent genes, that direct development and differentiation of stem cells, are found to be frequent targets of hypermethylation in cancers.ResultsHere we performed comprehensive analysis across multiple cancer types and identified that the decrease in H3K4me1 levels coincides with DNA hypermethylation at the bivalent promoter CGIs during tumorigenesis. Removal of DNA hypermethylation leads to increment of H3K4me1 at promoter CGIs with preference for bivalent genes. Nevertheless, the alteration of H3K4me1 by overexpressing or knockout LSD1, the demethylase of H3K4, doesn’t change the level or pattern of DNA methylation. Moreover, LSD1 was found to regulate the expression of a bivalent gene OVOL2 to promote tumorigenesis. Knockdown of OVOL2 in LSD1 knockout HCT116 cells restored the cancer cell phenotype.ConclusionIn summary, our work identified a universal indicator that can pre-mark DNA hypermethylation in cancer cells, and dissected the interplay between H3K4me1 and DNA hypermethylation in detail. Current study also reveals a novel mechanism underlying the oncogenic role of LSD1, providing clues for cancer therapies.

BackgroundSalt-alkali stress represents one of the most stressful events with deleterious consequences for plant growth and crop productivity. Despite studies focusing on the effects of salt-alkali stress on morphology and physiology, its molecular mechanisms remain unclear. Here, we employed RNA-sequencing (RNA-seq) to understand how Na2CO3 stress inhibits rice seedling growth.ResultsNa2CO3 stress significantly inhibited the growth of rice seedlings. Through RNA-seq, many differentially expressed genes (DEGs) were shown to be potentially involved in the rice seedling response to salt-alkali stress. After 1-day and 5-day treatments, RNA-seq identified 1780 and 2315 DEGs in the Na2CO3-treated versus -untreated rice seedling shoots, respectively. According to the gene ontology enrichment and the Kyoto Encylopedia of Genes and Genomes annotation of DEGs, the growth-inhibition processes associated with salt-alkali stress involve a myriad of molecular events, including biosynthesis and metabolism, enzyme activity, and binding, etc.ConclusionCollectively, the transcriptome analyses in the present work revealed several potential key regulators of plant response to salt-alkali stress, and might pave a way to improve salt-alkali stress tolerance in rice.

BackgroundDNA methylation plays important biological roles in plants and animals. To examine the rice genomic methylation landscape and assess its functional significance, we generated single-base resolution DNA methylome maps for Asian cultivated rice Oryza sativa ssp. japonica, indica and their wild relatives, Oryza rufipogon and Oryza nivara.ResultsThe overall methylation level of rice genomes is four times higher than that of Arabidopsis. Consistent with the results reported for Arabidopsis, methylation in promoters represses gene expression while gene-body methylation generally appears to be positively associated with gene expression. Interestingly, we discovered that methylation in gene transcriptional termination regions (TTRs) can significantly repress gene expression, and the effect is even stronger than that of promoter methylation. Through integrated analysis of genomic, DNA methylomic and transcriptomic differences between cultivated and wild rice, we found that primary DNA sequence divergence is the major determinant of methylational differences at the whole genome level, but DNA methylational difference alone can only account for limited gene expression variation between the cultivated and wild rice. Furthermore, we identified a number of genes with significant difference in methylation level between the wild and cultivated rice.ConclusionsThe single-base resolution methylomes of rice obtained in this study have not only broadened our understanding of the mechanism and function of DNA methylation in plant genomes, but also provided valuable data for future studies of rice epigenetics and the epigenetic differentiation between wild and cultivated rice.

BackgroundIn contrast to wild species, which have typically evolved phenotypes over long periods of natural selection, domesticates rapidly gained human-preferred agronomic traits in a relatively short-time frame via artificial selection. Under domesticated conditions, many traits can be observed that cannot only be due to environmental alteration. In the case of silkworms, aside from genetic divergence, whether epigenetic divergence played a role in domestication is an unanswered question. The silkworm is still an enigma in that it has two DNA methyltransferases (DNMT1 and DNMT2) but their functionality is unknown. Even in particular the functionality of the widely distributed DNMT1 remains unknown in insects in general.ResultsBy embryonic RNA interference, we reveal that knockdown of silkworm Dnmt1 caused decreased hatchability, providing the first direct experimental evidence of functional significance of insect Dnmt1. In the light of this fact and those that DNA methylation is correlated with gene expression in silkworms and some agronomic traits in domesticated organisms are not stable, we comprehensively compare silk gland methylomes of 3 domesticated (Bombyx mori) and 4 wild (Bombyx mandarina) silkworms to identify differentially methylated genes between the two. We observed 2-fold more differentiated methylated cytosinces (mCs) in domesticated silkworms as compared to their wild counterparts, suggesting a trend of increasing DNA methylation during domestication. Further study of more domesticated and wild silkworms narrowed down the domesticates’ epimutations, and we were able to identify a number of differential genes. One such gene showing demethyaltion in domesticates correspondently displays lower gene expression, and more interestingly, has experienced selective sweep. A methylation-increased gene seems to result in higher expression in domesticates and the function of its Drosophila homolog was previously found to be essential for cell volume regulation, indicating a possible correlation with the enlargement of silk glands in domesticated silkworms.ConclusionsOur results imply epigenetic influences at work during domestication, which gives insight into long time historical controversies regarding acquired inheritance.

BackgroundDNA methylation plays important biological roles in plants and animals. To examine the rice genomic methylation landscape and assess its functional significance, we generated single-base resolution DNA methylome maps for Asian cultivated rice Oryza sativa ssp. japonica, indica and their wild relatives, Oryza rufipogon and Oryza nivara.ResultsThe overall methylation level of rice genomes is four times higher than that of Arabidopsis. Consistent with the results reported for Arabidopsis, methylation in promoters represses gene expression while gene-body methylation generally appears to be positively associated with gene expression. Interestingly, we discovered that methylation in gene transcriptional termination regions (TTRs) can significantly repress gene expression, and the effect is even stronger than that of promoter methylation. Through integrated analysis of genomic, DNA methylomic and transcriptomic differences between cultivated and wild rice, we found that primary DNA sequence divergence is the major determinant of methylational differences at the whole genome level, but DNA methylational difference alone can only account for limited gene expression variation between the cultivated and wild rice. Furthermore, we identified a number of genes with significant difference in methylation level between the wild and cultivated rice.ConclusionsThe single-base resolution methylomes of rice obtained in this study have not only broadened our understanding of the mechanism and function of DNA methylation in plant genomes, but also provided valuable data for future studies of rice epigenetics and the epigenetic differentiation between wild and cultivated rice.

BackgroundIn contrast to wild species, which have typically evolved phenotypes over long periods of natural selection, domesticates rapidly gained human-preferred agronomic traits in a relatively short-time frame via artificial selection. Under domesticated conditions, many traits can be observed that cannot only be due to environmental alteration. In the case of silkworms, aside from genetic divergence, whether epigenetic divergence played a role in domestication is an unanswered question. The silkworm is still an enigma in that it has two DNA methyltransferases (DNMT1 and DNMT2) but their functionality is unknown. Even in particular the functionality of the widely distributed DNMT1 remains unknown in insects in general.ResultsBy embryonic RNA interference, we reveal that knockdown of silkworm Dnmt1 caused decreased hatchability, providing the first direct experimental evidence of functional significance of insect Dnmt1. In the light of this fact and those that DNA methylation is correlated with gene expression in silkworms and some agronomic traits in domesticated organisms are not stable, we comprehensively compare silk gland methylomes of 3 domesticated (Bombyx mori) and 4 wild (Bombyx mandarina) silkworms to identify differentially methylated genes between the two. We observed 2-fold more differentiated methylated cytosinces (mCs) in domesticated silkworms as compared to their wild counterparts, suggesting a trend of increasing DNA methylation during domestication. Further study of more domesticated and wild silkworms narrowed down the domesticates’ epimutations, and we were able to identify a number of differential genes. One such gene showing demethyaltion in domesticates correspondently displays lower gene expression, and more interestingly, has experienced selective sweep. A methylation-increased gene seems to result in higher expression in domesticates and the function of its Drosophila homolog was previously found to be essential for cell volume regulation, indicating a possible correlation with the enlargement of silk glands in domesticated silkworms.ConclusionsOur results imply epigenetic influences at work during domestication, which gives insight into long time historical controversies regarding acquired inheritance.