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Dana C Dolinoy Caren Weinhouse Tamara R Jones Laura S Rozek Randy L Jirtle 《Epigenetics》2010,5(7):637-644
The ability of environmental factors to shape health and disease involves epigenetic mechanisms that mediate gene-environment interactions. Metastable epiallele genes are variably expressed in genetically identical individuals due to epigenetic modifications established during early development. DNA methylation within metastable epialleles is stochastic due to probabilistic reprogramming of epigenetic marks during embryogenesis. Maternal nutrition and environment have been shown to affect metastable epiallele methylation patterns and subsequent adult phenotype. Little is known, however, about the role of histone modifications in influencing metastable epiallele expression and phenotypic variation. Utilizing chromatin immunoprecipitation followed by qPCR, we observe variable histone patterns in the 5′ long terminal repeat (LTR) of the murine viable yellow agouti (Avy) metastable epiallele. This region contains 6 CpG sites, which are variably methylated in isogenic Avy/a offspring. Yellow mice, which are hypomethylated at the Avy LTR and exhibit constitutive ectopic expression of Agouti (a), also display enrichment of H3 and H4 di-acetylation (p = 0.08 and 0.09, respectively). Pseudoagouti mice, in which Avy hypermethylation is thought to silence ectopic expression, exhibit enrichment of H4K20 tri-methylation (p = 0.01). No differences are observed for H3K4 tri-methylation (p = 0.7), a modification often enriched in the promoter of active genes. These results show for the first time the presence of variable histone modifications at a metastable epiallele, indicating that DNA methylation acts in concert with histone modifications to affect inter-individual variation of metastable epiallele expression. Therefore, the potential for environmental factors to influence histone modifications, in addition to DNA methylation, should be addressed in environmental epigenomic studies.Key words: epigenetics, metastable epiallele, viable yellow agouti, histone, environmental epigenomics 相似文献
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Roles,and establishment,maintenance and erasing of the epigenetic cytosine methylation marks in plants 总被引:1,自引:0,他引:1
Heritable information in plants consists of genomic information in DNA sequence and epigenetic information superimposed on DNA sequence. The latter is in the form of cytosine methylation at CG, CHG and CHH elements (where H = A, T or C) and a variety of histone modifications in nucleosomes. The epialleles arising from cytosine methylation marks on the nuclear genomic loci have better heritability than the epiallelic variation due to chromatin marks. Phenotypic variation is increased manifold by epiallele comprised methylomes. Plants (angiosperms) have highly conserved genetic mechanisms to establish, maintain or erase cytosine methylation from epialleles. The methylation marks in plants fluctuate according to the cell/tissue/organ in the vegetative and reproductive phases of plant life cycle. They also change according to environment. Epialleles arise by gain or loss of cytosine methylation marks on genes. The changes occur due to the imperfection of the processes that establish and maintain the marks and on account of spontaneous and stress imposed removal of marks. Cytosine methylation pattern acquired in response to abiotic or biotic stress is often inherited over one to several subsequent generations. Cytosine methylation marks affect physiological functions of plants via their effect(s) on gene expression levels. They also repress transposable elements that are abundantly present in plant genomes. The density of their distribution along chromosome lengths affects meiotic recombination rate, while their removal increases mutation rate. Transposon activation due to loss of methylation causes rearrangements such that new gene regulatory networks arise and genes for microRNAs may originate. Cytosine methylation dynamics contribute to evolutionary changes. This review presents and discusses the available evidence on origin, removal and roles of cytosine methylation and on related processes, such as RNA directed DNA methylation, imprinting, paramutation and transgenerational memory in plants. 相似文献
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Waterland RA Dolinoy DC Lin JR Smith CA Shi X Tahiliani KG 《Genesis (New York, N.Y. : 2000)》2006,44(9):401-406
Transient environmental exposures during mammalian development can permanently alter gene expression and metabolism by influencing the establishment of epigenetic gene regulatory mechanisms. The genomic characteristics that confer such epigenetic plasticity upon specific loci, however, have not been characterized. Methyl donor supplementation of female mice before and during pregnancy permanently increases DNA methylation at the viable yellow agouti (A(vy)) metastable epiallele in the offspring. The current study tested whether another murine metastable epiallele, axin fused (Axin(Fu)), similarly exhibits epigenetic plasticity to maternal diet. We found that methyl donor supplementation of female mice before and during pregnancy increased DNA methylation at Axin(Fu) and thereby reduced by half the incidence of tail kinking in Axin(Fu)/+ offspring. The hypermethylation was tail-specific, suggesting a mid-gestation effect. Our results indicate that stochastic establishment of epigenotype at metastable epialleles is, in general, labile to methyl donor nutrition, and such influences are not limited to early embryonic development. 相似文献
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《Epigenetics》2013,8(7):637-644
The ability of environmental factors to shape health and disease involves epigenetic mechanisms that mediate gene-environment interactions. Metastable epiallele genes are variably expressed in genetically identical individuals due to epigenetic modifications established during early development. DNA methylation within metastable epialleles is stochastic due to probabilistic reprogramming of epigenetic marks during embryogenesis. Maternal nutrition and environment have been shown to affect metastable epiallele methylation patterns and subsequent adult phenotype. Little is known, however, about the role of histone modifications in influencing metastable epiallele expression and phenotypic variation. Utilizing chromatin immunoprecipitation followed by qPCR, we observe variable histone patterns in the 5’ long terminal repeat (LTR) of the murine viable yellow agouti (Avy) metastable epiallele. This region contains 6 CpG sites, which are variably methylated in isogenic Avy/a offspring. Yellow mice, which are hypomethylated at the Avy LTR and exhibit constitutive ectopic expression of agouti (a), also display enrichment of H3 and H4 di-acetylation (p=0.08 and 0.09, respectively). Pseudoagouti mice, in which Avy hypermethylation is thought to silence ectopic expression, exhibit enrichment of H4K20 tri-methylation (p=0.01). No differences are observed for H3K4 tri-methylation (p=0.7), a modification often enriched in the promoter of active genes. These results show for the first time the presence of variable histone modifications at a metastable epiallele, indicating that DNA methylation acts in concert with histone modifications to affect inter-individual variation of metastable epiallele expression. Therefore, the potential for environmental factors to influence histone modifications, in addition to DNA methylation, should be addressed in environmental epigenomic studies. 相似文献
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In the green alga, Chlamydomonas, chloroplast DNA is maternally transmitted to the offspring. We previously hypothesized that the underlying molecular mechanism involves specific methylation of maternal gamete DNA before mating, protecting against degradation. To obtain direct evidence for this, we focused on a DNA methyltransferase, DMT1, which was previously shown to be localized in chloroplasts. The full-length DMT1 protein with a molecular mass of 150 kD was expressed in insect cells, and its catalytic activity was determined. In vitro assays using synthetic DNA indicated methylation of all cytosine residues, with no clear selectivity in terms of the neighboring nucleotides. Subsequently, transgenic paternal cells constitutively expressing DMT1 were constructed and direct methylation mapping assays of their DNA showed a clear nonselective methylation of chloroplast DNA. When transgenic paternal cells were crossed with wild-type maternal cells, the frequency of biparental and paternal offspring of chloroplasts increased up to 23% while between wild-type strains it was approximately 3%. The results indicate that DMT1 is a novel type of DNA methyltransferase with a nonselective cytosine methylation activity, and that chloroplast DNA methylation by DMT1 is one of factors influencing maternal inheritance of chloroplast genes. 相似文献
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In plants, naturally occurring methylation of genes can affect the level of gene expression. Variation among individuals in the degree of methylation of a gene, termed epialleles, produces novel phenotypes that are heritable across generations. To date, ecologically important genes with methylated epialleles have been found to affect floral shape, vegetative and seed pigmentation, pathogen resistance and development in plants. Currently, the extent to which epiallelic variation is an important common contributor to phenotypic variation in natural plant populations and its fitness consequences are not known. Because epiallele phenotypes can have identical underlying DNA sequences, response to selection on these phenotypes is likely to differ from expectations based on traditional models of microevolution. Research is needed to understand the role of epialleles in natural plant populations. Recent advances in molecular genetic techniques could enable population biologists to screen for epiallelic variants within plant populations and disentangle epigenetic from more standard genetic sources of phenotypic variance, such as additive genetic variance, dominance variance, epistasis and maternal genetic effects. 相似文献
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From nucleotide sequences of mitochondrial and chloroplast genes the probable frequency of the CpG----TpG + CpA substitutions was determined. These substitutions may indicate the level of prior DNA methylation. It was found that the level of this methylation is significantly lower in mitochondrial DNA (mtDNA) and chloroplast DNA (chDNA) than in nuclear DNA (nDNA) of the same species. The species (taxon) specificity of mtDNA and chDNA methylation was revealed. A correlation was found between the level of CpG methylation in nDNA, and mtDNA and chDNA in different organisms. It is shown that cytosine residues in CpG were not subjected to significant methylation in the fungi and invertebrate mtDNA and also in the algae chDNA. In contrast, the vertebrate mtDNA bears the impress of CpG-supression, which is confirmed by direct data on methylation of these DNA. Here the first data on the possible enzymatic methylation of the plant mtDNA and chDNA were obtained. It was shown that the degree of CpG-suppression in the 5S rRNA nuclear genes of lower and higher plants is significantly higher in the chloroplast genes of 4,5S and 5S rRNA. From data on pea chDNA hydrolysis with MspI and HpaII it was established that in CCGG sequences this DNA is not methylated. The role of DNA methylation in increasing the mutation rate and in accelerating the evolutionary rates of vertebrate mtDNA is discussed. 相似文献
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Ionic and osmotic effects of salinity on the ultrastructure of chloroplasts in salt-treated rice seedlings were investigated. After rice seedlings were grown in hydroponic culture for three weeks, they were treated with NaCl and polyethylene glycol (PEG) 4000 both at a water potential of -1.0 MPa for 3 days. The most notable difference in ultrastructural change between NaCl and PEG treatment was observed in the damage in chloroplast membranes. NaCl induced swelling of thylakoids and caused only a slight destruction of the chloroplast envelope. PEG caused severe destruction of the chloroplast envelope compared with NaCl, however thylakoids did not swell. Our observations suggested that in salt-treated rice plants, the ionic effects induced swelling of thylakoids and the osmotic effects caused the destruction of chloroplast envelope. 相似文献
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The inheritance of chloroplast genes in Chlamydomonas is regulated by methylation of chloroplast DNA during gametogenesis. The wild-type pattern of maternal inheritance results from the methylation of chloroplast DNA in female (mt+) but not in male (mt-) gametes, leading to preferential degradation of chloroplast DNA of male origin in zygotes. This paper describes the distribution of 5-methyl cytosine residues in restriction fragments of chloroplast DNA sampled during gametogenesis by two methods: ethidium bromide staining of agarose gels, and binding of antibody directed against 5-methyl cytosine onto restriction fragments blotted to nitro-cellulose paper. Methylated cytosines are located in most if not all Eco RI and Msp I fragments, but the extent of methylation is not proportional to fragment size. The mat-1 mutation carried by males converts maternal inheritance. Chloroplast DNA of male gametes carrying the mat-1 mutation becomes methylated during gametogenesis. This methylation protects against restriction enzyme-promoted degradation in zygotes, as shown by physical data demonstrating the transmission to progeny of chloroplast genes carried on chloroplast DNA of the mat-1 male parent. Thus the mat-1 gene, which is linked to the mating-type locus, determines whether or not methylation of chloroplast DNA will occur in males during gametogenesis. 相似文献
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Heritable epigenetic variants of genes, termed epialleles, can broaden genetic and phenotypic diversity in eukaryotes. Epialleles may also provide a new source of beneficial traits for crop breeding, but very few epialleles related to agricultural traits have been identified in crops. Here, we identified Epi-rav6, a gain-of-function epiallele of rice (Oryza sativa) RELATED TO ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1) 6 (RAV6), which encodes a B3 DNA-binding domain-containing protein. The Epi-rav6 plants show larger lamina inclination and smaller grain size; these agronomically important phenotypes are inherited in a semidominant manner. We did not find nucleotide sequence variation of RAV6. Instead, we found hypomethylation in the promoter region of RAV6, which caused ectopic expression of RAV6 in Epi-rav6 plants. Bisulfite analysis revealed that cytosine methylation of four CG and two CNG loci within a continuous 96-bp region plays essential roles in regulating RAV6 expression; this region contains a conserved miniature inverted repeat transposable element transposon insertion in cultivated rice genomes. Overexpression of RAV6 in the wild type phenocopied the Epi-rav6 phenotype. The brassinosteroid (BR) receptor BR INSENSITIVE1 and BR biosynthetic genes EBISU DWARF, DWARF11, and BR-DEFICIENT DWARF1 were ectopically expressed in Epi-rav6 plants. Also, treatment with a BR biosynthesis inhibitor restored the leaf angle defects of Epi-rav6 plants. This indicates that RAV6 affects rice leaf angle by modulating BR homeostasis and demonstrates an essential regulatory role of epigenetic modification on a key gene controlling important agricultural traits. Thus, our work identifies a unique rice epiallele, which may represent a common phenomenon in complex crop genomes.Epigenetic gene variants (epialleles) carry heritable changes in gene expression that do not result from alterations in the underlying DNA sequence (Kakutani, 2002). In eukaryotes, cytosine DNA methylation, a conserved epigenetic mark, plays essential roles in the silencing of transposable elements (TEs) and genes (Law and Jacobsen, 2010). In higher plants, the few known epialleles involve alterations in DNA methylation, indicating that this epigenetic marker makes a large contribution to epigenetic diversity. The Arabidopsis (Arabidopsis thaliana) clark kent epiallele, which has hypermethylated cytosines at the SUPERMAN locus, causes increased numbers of stamens and carpels (Jacobsen and Meyerowitz, 1997). Also, DNA hypomethylation at two direct repeats in the promoter region of FLOWERING WAGENINGEN (FWA; Soppe et al., 2000) causes the late-flowering phenotype in Arabidopsis plants carrying the fwa epiallele. Plants carrying the natural epiallele hypermethylated at Linaria cycloidea-like show altered floral symmetry, from bilateral to radial, in Linaria vulgaris (Cubas et al., 1999). In tomato (Solanum lycopersicum), the Colorless nonripening phenotype results from hypermethylation at the promoter of SQUAMOSA promoter-binding protein like (Manning et al., 2006). In melon (Cucumis melo), the transition from male to female flowers results from DNA hypermethylation in the promoter of CmWIP1, as mediated by a transposon insertion in gynoecious varieties (Martin et al., 2009).Work in rice (Oryza sativa) has found only two epialleles, Epi-d1 and Epi-df, both of which show a dwarf phenotype (Miura et al., 2009; Zhang et al., 2012). Epi-d1 is a spontaneous epiallele that shows a metastable dwarf phenotype caused by DNA hypermethylation in the promoter region of DWARF1 (Miura et al., 2009). Epi-df is a gain-of-function epiallele caused by hypomethylation in the 5′ region of FERTILIZATION-INDEPENDENT ENDOSPERM1 (FIE1). The ectopic expression of FIE1 in Epi-df results in dwarf and various floral defects that are inherited in a dominant manner (Zhang et al., 2012).In Arabidopsis, DNA methylation occurs in three sequence contexts: CG, CHG, and CHH (where H = A, C, or T) catalyzed by the de novo DNA methyltransferase DOMAINS REARRANGED METHYLASE2 (DRM2; Cao and Jacobsen, 2002). In the symmetrical contexts, DNA METHYLTRANSFERASE1 (MET1) and CHROMOMETHYLASE3 maintain methylation in the CG and CHG contexts, respectively (Lindroth et al., 2001; Law and Jacobsen, 2010). Small interfering RNAs trigger de novo methylation in all sequence contexts and also trigger the maintenance of CHH methylation via RNA-directed DNA methylation predominately mediated by DRM2 (Cao and Jacobsen, 2002; Law and Jacobsen, 2010).DNA methylation may be more prevalent and important in rice than in Arabidopsis, owing to the large numbers of TEs in the rice genome. In fact, Arabidopsis mutants of various DNA methyltransferases or DECREASE IN DNA METHYLATION1 show few or no developmental defects (Vongs et al., 1993; Lindroth et al., 2001; Cao and Jacobsen, 2002; Saze et al., 2003). By contrast, the rice met1a null mutant shows either viviparous germination or early embryonic lethality (Hu et al., 2014; Yamauchi et al., 2014). Moreover, impairment of the RNA-directed DNA methylation pathway proteins Dicer-like 3a and DRM2 causes drastic and pleiotropic developmental phenotypes (Moritoh et al., 2012; Wei et al., 2014).Leaf angle is an important agronomic trait that directly affects crop architecture and grain yields (Sinclair and Sheehy, 1999). Crops with erect leaves capture more light for photosynthesis and are suitable for dense planting, all of which increase yields (Sakamoto et al., 2006). In rice, the brassinosteroid (BR) phytohormones participate in the determination of leaf angle (Tong and Chu, 2012; Zhang et al., 2014). BR-deficient or BR-insensitive mutants display erect leaves, while overexpression of BR biosynthesis genes or signaling components results in less erect leaves with large leaf inclination (Yamamuro et al., 2000; Hong et al., 2005; Bai et al., 2007). For example, loss-of-function mutants of rice BR INSENSITIVE1 (OsBRI1) and EBISU DWARF (D2), which encode the rice BR receptor kinase and a BR synthesis enzyme, respectively, show erect leaves (Yamamuro et al., 2000; Hong et al., 2003). In rice, RELATED TO ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1; RAV)-LIKE1 (RAVL1), a B3 DNA-binding domain-containing protein, maintains BR homeostasis via the coordinated activation of BRI1 and BR biosynthetic genes D2, DWARF11 (D11), and BR-DEFICIENT DWARF1 (BRD1; Je et al., 2010). The ravl1 mutant and RAVL1 overexpression lines showed erect leaves and large leaf angles, respectively (Je et al., 2010).Here, we identified a natural epiallele of rice RAV6 and found that plants carrying this epiallele show increased leaf angle and small grains, as well as hypomethylation in the RAV6 promoter region and ectopic expression of RAV6. Our work revealed that epigenetic modification of RAV6 plays an essential role in the regulation of important agricultural traits in rice and found that RAV6 acts via BR homeostasis. 相似文献
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Muniandy Kanagesswari Tan Mun Hua Song Beng Kah Ayub Qasim Rahman Sadequr 《Plant molecular biology》2019,100(1-2):33-46
Plant Molecular Biology - Grain amyloplast and leaf chloroplast DNA sequences are identical in rice plants but are differentially methylated. The leaf chloroplast DNA becomes more methylated as the... 相似文献
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Extensive methylation of chloroplast DNA by a nuclear gene mutation does not affect chloroplast gene transmission in chlamydomonas 总被引:1,自引:0,他引:1
Paul L. Bolen David M. Grant David Swinton John E. Boynton Nicholas W. Gillham 《Cell》1982,28(2):335-343
Based on analysis by high pressure liquid chromatography, greater than 35% of the cytosine residues in chloroplast DNA of vegetative cells were found to be methylated constitutively in the nuclear gene mutation (me-1) of Chlamydomonas reinhardtii, which has an otherwise wild-type phenotype. Digestion of chloroplast DNA from vegetative cells and gametes of this mutant with restriction endonucleases Hpa II and Msp I reveals that in the 5′CCGG3′ sequence, CpG is methylated extensively, whereas CpC is only methylated occasionally. Hae III (5′GGCC3′) digestion of the mutant chloroplast DNA also shows extensive methylation of the GpC sequence. In contrast to the results of Sager and colleagues, which show a correlation between methylation of chloroplast DNA and transmission of chloroplast genes in crosses, our results with crosses of the me-1 mutant suggest that extensive chloroplast DNA methylation may be insufficient to account for the pattern of inheritance of chloroplast genes in Chlamydomonas. 相似文献
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Caren Weinhouse Olivia S Anderson Tamara R Jones Jung Kim Shayna A Liberman Muna S Nahar Laura S Rozek Randy L Jirtle Dana C Dolinoy 《Epigenetics》2011,6(9):1105-1113
Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) metastable epiallele exhibits stochastic DNA methylation and histone modifications associated with coat color variation in isogenic individuals. The distribution of Avy variable expressivity shifts following maternal nutritional and environmental exposures. To characterize additional murine metastable epialleles, we utilized genome-wide expression arrays (N = 10 male individuals, 3 tissues per individual) and identified candidates displaying large variability in gene expression among individuals (Vi = inter-individual variance), concomitant with a low variability in gene expression across tissues from the three germ layers (Vt = inter-tissue variance), two features characteristic of the Avy metastable epiallele. The CpG island in the promoter of Dnajb1 and two contraoriented ERV class II repeats in Glcci1 were validated to display underlying stochasticity in methylation patterns common to metastable epialleles. Furthermore, liver DNA methylation in mice exposed in utero to 50 mg bisphenol A (BPA)/kg diet (N = 91) or a control diet (N = 79) confirmed environmental lability at validated candidate genes. Significant effects of exposure on mean CpG methylation were observed at the Glcci1 Repeat 1 locus (p < 0.0001). Significant effects of BPA also were observed at the first and fifth CpG sites studied in Glcci1 Repeat 2 (p < 0.0001 and p = 0.004, respectively). BPA did not affect methylation in the promoter of Dnajb1 (p = 0.59). The characterization of metastable epialleles in humans is crucial for the development of novel screening and therapeutic targets for human disease prevention.Key words: epigenetics, metastable epiallele, viable yellow agouti, environmental epigenomics 相似文献
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Jinbin Wang Xiaochong Li Qianli Dong Changping Li Juzuo Li Ning Li Baoxu Ding Xiaofei Wang Yanan Yu Tianya Wang Zhibin Zhang Yiyang Yu Man Lang Zixian Zeng Bao Liu Lei Gong 《植物学报(英文版)》2022,64(12):2396-2410
Associations between 3D chromatin architectures and epigenetic modifications have been characterized in animals.However,any impact of DNA methylation on chromatin architecture in plants is understudied,which is confined to Arabidopsis thaliana.Because plant species differ in genome size,composition,and overall chromatin packing,it is unclear to what extent findings from A.thaliana hold in other species.Moreover,the incomplete chromatin architectural profiles and the low-resolution high-throughpu... 相似文献
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重金属对水稻和小麦DNA甲基化水平的影响 总被引:25,自引:0,他引:25
和对照相比,0.025(或0.05)-0.1mmol/L的Cu^2 (或0.05)-1.0mmol/L的Cd^2 或Hg^2 导致水稻(或小麦)叶DNA中的5-甲基胞嘧啶百分含量大幅度上升;当Cu^2 浓度>0.1mmol/L时,小麦和水稻叶DNA中5-甲基胞嘧啶的百分含量随Cu^2 浓度的增高略有下降,但仍高于对照。0.1-1.0mmol/L的Cu^2 ,Cd^2 和Hg^2 也导致小麦穗DNA为5-甲基胞嘧啶的百分含量随Cu^2 ,Cd^ 和Cd^2 能使小麦和水稻根系DNA中5-甲基胞嘧啶的百分含量显著高于对照,而0.1-1.0mmol/L的Hg^2 以及1.0mmol/L的Cu^2 和Cd^2 则造成小麦和水稻根系DNA中5-甲基胞嘧啶的百分含量显著低于对照。 相似文献