The maize methylome influences mRNA splice sites and reveals widespread paramutation-like switches guided by small RNA

Regulski, Michael; Lu, Zhenyuan; Kendall, Jude; Donoghue, Mark T.A.; Reinders, Jon; Llaca, Víctor; Deschamps, Stéphane; Smith, Andrew D.; Levy, Dan; McCombie, W. Richard; Tingey, Scott V.; Rafalski, Antoni; Hicks, James; Ware, Doreen; Martienssen, Robert A.

doi:10.1101/gr.153510.112

Cited by 255 publications

(355 citation statements)

References 49 publications

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“…7B). The difference in specificity of splicing factor gene expression changes compared with splicing changes likely arises due to the influence of other factors on splicing, such as transcription rate or methylation status (Kornblihtt et al, 2004;Shepard and Hertel, 2008;Regulski et al, 2013). It has been shown previously that splicing factors are frequently alternatively spliced, often resulting in increased or decreased NMD sensitivity (Lareau and Brenner, 2015).…”

Section: Changes In Splicing Correlate With Gene Expression Changes Imentioning

confidence: 99%

“…Gene expression changes in splicing factors also play key roles in guiding tissuespecific developmental processes, including seed development, where the U2AF splicing factor ROUGH ENDOSPERM3 has been shown to be involved in mediating the interaction between the embryo and endosperm (Fouquet et al, 2011). The control of these alternative splicing differences among different tissues is thought to be the result of differential splicing factor expression and is likely also influenced by tissue-specific methylation patterns (Regulski et al, 2013). Alternative splicing has also been tied closely with nonsensemediated decay (NMD) and has been shown to increase or decrease a transcript's sensitivity to this decay mechanism under a variety of conditions (Kalyna et al, 2012;Drechsel et al, 2013;Staiger and Brown, 2013).…”

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confidence: 99%

“…Trans-acting factors also exert a strong effect on splicing and are mostly composed of Ser/Arg-rich proteins, which typically promote intron removal, and heterogenous nuclear ribonucleoproteins, which typically inhibit it (Erkelenz et al, 2013). A host of other indirect factors can affect splicing, including transcription rate, methylation status, and any cellular conditions that alter RNA secondary structure (Kornblihtt et al, 2004;Shepard and Hertel, 2008;Regulski et al, 2013). These different factors combine to determine the suite of isoforms that a gene produces in a given tissue, developmental stage, and environment.…”

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Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

et al. 2015

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Alternative splicing plays a crucial role in plant development as well as stress responses. Although alternative splicing has been studied during development and in response to stress, the interplay between these two factors remains an open question. To assess the effects of drought stress on developmentally regulated splicing in maize (Zea mays), 94 RNA-seq libraries from ear, tassel, and leaf of the B73 public inbred line were constructed at four developmental stages under both well-watered and drought conditions. This analysis was supplemented with a publicly available series of 53 libraries from developing seed, embryo, and endosperm. More than 48,000 novel isoforms, often with stage-or condition-specific expression, were uncovered, suggesting that developmentally regulated alternative splicing occurs in thousands of genes. Drought induced large developmental splicing changes in leaf and ear but relatively few in tassel. Most developmental stage-specific splicing changes affected by drought were tissue dependent, whereas stage-independent changes frequently overlapped between leaf and ear. A linear relationship was found between gene expression changes in splicing factors and alternative spicing of other genes during development. Collectively, these results demonstrate that alternative splicing is strongly associated with tissue type, developmental stage, and stress condition.After transcription, the majority of eukaryotic premRNA is subjected to a series of posttranscriptional modifications, including the removal of introns to form a mature mRNA (Stamm et al., 2005). Although some introns are removed constitutively, many can be processed in a variety of alternative ways, including exon skipping, intron retention, alternative acceptor, alternative donor, and alternative position (change in both acceptor and donor positions; Lorkovic et al., 2000). These alternative splicing events form a crucial regulatory level and have the ability to alter an mRNA's stability, localization, and protein products. Alternative splicing events are controlled by a variety of cis-elements, including the presence of consensus splice sequences at the intron-exon border and intronic and exonic splicing enhancer sequences (Pertea et al., 2007). Trans-acting factors also exert a strong effect on splicing and are mostly composed of Ser/Arg-rich proteins, which typically promote intron removal, and heterogenous nuclear ribonucleoproteins, which typically inhibit it (Erkelenz et al., 2013). A host of other indirect factors can affect splicing, including transcription rate, methylation status, and any cellular conditions that alter RNA secondary structure (Kornblihtt et al

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Section: Changes In Splicing Correlate With Gene Expression Changes Imentioning

confidence: 99%

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confidence: 99%

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Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

et al. 2015

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“…These results suggest that alteration of the DNA methylation status in these genes can change the activities of the anthocyanin biosynthetic pathway. Furthermore, genome-wide methylome analysis in maize and rice has suggested that the DNA methylation in the promoter region often represses gene expression, whereas moderate gene-body methylation has a positive effect on the gene expression (Li et al, 2012;Regulski et al, 2013). Therefore, DNA methylation status may affect gene expression.…”

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confidence: 99%

The Birth of a Black Rice Gene and Its Local Spread by Introgression

et al. 2015

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The origin and spread of novel agronomic traits during crop domestication are complex events in plant evolution. Wild rice (Oryza rufipogon) has red grains due to the accumulation of proanthocyanidins, whereas most cultivated rice (Oryza sativa) varieties have white grains induced by a defective allele in the Rc basic helix-loop-helix (bHLH) gene. Although the events surrounding the origin and spread of black rice traits remain unknown, varieties with black grains due to anthocyanin accumulation are distributed in various locations throughout Asia. Here, we show that the black grain trait originated from ectopic expression of the Kala4 bHLH gene due to rearrangement in the promoter region. Both the Rc and Kala4 genes activate upstream flavonol biosynthesis genes, such as chalcone synthase and dihydroflavonol-4-reductase, and downstream genes, such as leucoanthocyanidin reductase and leucoanthocyanidin dioxygenase, to produce the respective specific pigments. Genome analysis of 21 black rice varieties as well as red-and white-grained landraces demonstrated that black rice arose in tropical japonica and its subsequent spread to the indica subspecies can be attributed to the causal alleles of Kala4. The relatively small size of genomic fragments of tropical japonica origin in some indica varieties indicates that refined introgression must have occurred by natural crossbreeding in the course of evolution of the black trait in rice.

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“…Plant DNA methylation is known to play an important role in genomic imprinting and genomic protection from transposable elements (TEs) and other repetitive DNA sequences. Furthermore, it regulates the expression of multiple genes (Jaenisch and Bird, 2003) and has been implied to play a role in gene splicing (Regulski et al, 2013). The influence of DNA methylation on development is especially evident in the case of mutations in DMT genes, which are embryo lethal in mice and lead to developmental abnormalities in plants (Goll and Bestor, 2005).…”

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Differential Methylation during Maize Leaf Growth Targets Developmentally Regulated Genes

et al. 2014

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DNA methylation is an important and widespread epigenetic modification in plant genomes, mediated by DNA methyltransferases (DMTs). DNA methylation is known to play a role in genome protection, regulation of gene expression, and splicing and was previously associated with major developmental reprogramming in plants, such as vernalization and transition to flowering. Here, we show that DNA methylation also controls the growth processes of cell division and cell expansion within a growing organ. The maize (Zea mays) leaf offers a great tool to study growth processes, as the cells progressively move through the spatial gradient encompassing the division zone, transition zone, elongation zone, and mature zone. Opposite to de novo DMTs, the maintenance DMTs were transcriptionally regulated throughout the growth zone of the maize leaf, concomitant with differential CCGG methylation levels in the four zones. Surprisingly, the majority of differentially methylated sequences mapped on or close to gene bodies and not to repeat-rich loci. Moreover, especially the 59 and 39 regions of genes, which show overall low methylation levels, underwent differential methylation in a developmental context. Genes involved in processes such as chromatin remodeling, cell cycle progression, and growth regulation, were differentially methylated. The presence of differential methylation located upstream of the gene anticorrelated with transcript expression, while gene body differential methylation was unrelated to the expression level. These data indicate that DNA methylation is correlated with the decision to exit mitotic cell division and to enter cell expansion, which adds a new epigenetic level to the regulation of growth processes.DNA methylation is the covalent modification of nucleotides in DNA by the addition of a methyl group. In the nuclear genome of higher eukaryotes, 5-methylcytosine is the most important DNA modification (Goll and Bestor, 2005). It is a phenomenon of ancient origin predating plant-animal diversification. However, some differences exist between plant and animal methylome patterning and function, and DNA methylation has been found to be evolutionarily lost in a few species (Feng et al., 2010;Zemach et al., 2010). Eukaryotic DNA methylation is established by DNA methyltransferase (DMT) enzymes that transfer a methyl group from S-adenosyl Met to the fifth carbon of cytosine. These enzymes can largely be subdivided in maintenance and de novo DMTs, depending on whether the recognition site is already methylated or not. Maintenance DMTs conserve the methylation status of symmetrical (palindromic) sites after DNA replication, by recognizing the hemimethylated locus and methylating the newly synthesized strand. In plants, there are two types of maintenance DMTs: DNA METHYLTRANSFERASE (MET) and CHROMOMETHYLASE (CMT). The former methylates CG sites during DNA replication, whereas the latter methylates CHG (H = A, C, or T) sites located in chromatin in which histone 3 is dimethylated on Lys-9 (Goll and Bestor, 2005). De no...

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The maize methylome influences mRNA splice sites and reveals widespread paramutation-like switches guided by small RNA

Cited by 255 publications

References 49 publications

Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

Genome-Wide Analysis of Alternative Splicing during Development and Drought Stress in Maize

The Birth of a Black Rice Gene and Its Local Spread by Introgression

Differential Methylation during Maize Leaf Growth Targets Developmentally Regulated Genes

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