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A position effect on the heritability of epigenetic silencing.

Singh J, Freeling M, Lisch D - PLoS Genet. (2008)

Bottom Line: In animals and yeast, position effects have been well documented.In contrast, there are few examples of position effects in plants, and there are no documented examples in either plants or animals for positions that are associated with the reversal of previously established silenced states.To our knowledge, this is the first documented example of a position effect that is associated with the reversal of epigenetic silencing.

View Article: PubMed Central - PubMed

Affiliation: Plant Science Department, McGill University, Macdonald Campus, Ste Anne de Bellevue, Quebec, Canada.

ABSTRACT
In animals and yeast, position effects have been well documented. In animals, the best example of this process is Position Effect Variegation (PEV) in Drosophila melanogaster. In PEV, when genes are moved into close proximity to constitutive heterochromatin, their expression can become unstable, resulting in variegated patches of gene expression. This process is regulated by a variety of proteins implicated in both chromatin remodeling and RNAi-based silencing. A similar phenomenon is observed when transgenes are inserted into heterochromatic regions in fission yeast. In contrast, there are few examples of position effects in plants, and there are no documented examples in either plants or animals for positions that are associated with the reversal of previously established silenced states. MuDR transposons in maize can be heritably silenced by a naturally occurring rearranged version of MuDR. This element, Muk, produces a long hairpin RNA molecule that can trigger DNA methylation and heritable silencing of one or many MuDR elements. In most cases, MuDR elements remain inactive even after Muk segregates away. Thus, Muk-induced silencing involves a directed and heritable change in gene activity in the absence of changes in DNA sequence. Using classical genetic analysis, we have identified an exceptional position at which MuDR element silencing is unstable. Muk effectively silences the MuDR element at this position. However, after Muk is segregated away, element activity is restored. This restoration is accompanied by a reversal of DNA methylation. To our knowledge, this is the first documented example of a position effect that is associated with the reversal of epigenetic silencing. This observation suggests that there are cis-acting sequences that alter the propensity of an epigenetically silenced gene to remain inactive. This raises the interesting possibility that an important feature of local chromatin environments may be the capacity to erase previously established epigenetic marks.

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Related in: MedlinePlus

A representation of the region into which MuDR(p5) is inserted.Sequences in yellow represent the target site duplication that was produced upon insertion. Sequences in green are the GA-rich sequences identified near the insertion. Sequences in red are presumed coding sequences. The rice homolog is the gene that best matches the Hemera gene in maize.
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pgen-1000216-g010: A representation of the region into which MuDR(p5) is inserted.Sequences in yellow represent the target site duplication that was produced upon insertion. Sequences in green are the GA-rich sequences identified near the insertion. Sequences in red are presumed coding sequences. The rice homolog is the gene that best matches the Hemera gene in maize.

Mentions: Given its propensity to reactivate, we were particularly interested in sequences flanking MuDR(p5). This element was inserted into the 5′ UTR just 4 base pairs proximal to the start codon of a putative ORF of unknown function (Figure 10), which we designate here Hemera, after the Greek goddess of the day, who was believed to disperse the night's mist each morning. Genes homologous to Hemera can be detected other grasses such as rice and Brachypodium distachyon. This conservation, along with the presence cDNA sequences in the database from several species, including maize, suggests that this gene is functional. The insertion of MuDR(p5) was 69 bp downstream of a 37 bp GA-rich sequence composed largely of GA repeats. Interestingly, although the rice and B. distachyon 5′ UTRs are not homologous to the maize sequence by sequence similarity, each of them has a GA-rich sequence roughly the same distance from the putative start of translation. These data suggest that sequence composition, rather than sequence order, may be conserved at this gene in these three species. Homologues of Hemera are also present in dicots, including papaya, grape, Arabidopsis and poplar. Although some of these sequences carry GA or TC rich regions near the putative start of translation, their positions are not conserved between species (Figure S1).


A position effect on the heritability of epigenetic silencing.

Singh J, Freeling M, Lisch D - PLoS Genet. (2008)

A representation of the region into which MuDR(p5) is inserted.Sequences in yellow represent the target site duplication that was produced upon insertion. Sequences in green are the GA-rich sequences identified near the insertion. Sequences in red are presumed coding sequences. The rice homolog is the gene that best matches the Hemera gene in maize.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2563033&req=5

pgen-1000216-g010: A representation of the region into which MuDR(p5) is inserted.Sequences in yellow represent the target site duplication that was produced upon insertion. Sequences in green are the GA-rich sequences identified near the insertion. Sequences in red are presumed coding sequences. The rice homolog is the gene that best matches the Hemera gene in maize.
Mentions: Given its propensity to reactivate, we were particularly interested in sequences flanking MuDR(p5). This element was inserted into the 5′ UTR just 4 base pairs proximal to the start codon of a putative ORF of unknown function (Figure 10), which we designate here Hemera, after the Greek goddess of the day, who was believed to disperse the night's mist each morning. Genes homologous to Hemera can be detected other grasses such as rice and Brachypodium distachyon. This conservation, along with the presence cDNA sequences in the database from several species, including maize, suggests that this gene is functional. The insertion of MuDR(p5) was 69 bp downstream of a 37 bp GA-rich sequence composed largely of GA repeats. Interestingly, although the rice and B. distachyon 5′ UTRs are not homologous to the maize sequence by sequence similarity, each of them has a GA-rich sequence roughly the same distance from the putative start of translation. These data suggest that sequence composition, rather than sequence order, may be conserved at this gene in these three species. Homologues of Hemera are also present in dicots, including papaya, grape, Arabidopsis and poplar. Although some of these sequences carry GA or TC rich regions near the putative start of translation, their positions are not conserved between species (Figure S1).

Bottom Line: In animals and yeast, position effects have been well documented.In contrast, there are few examples of position effects in plants, and there are no documented examples in either plants or animals for positions that are associated with the reversal of previously established silenced states.To our knowledge, this is the first documented example of a position effect that is associated with the reversal of epigenetic silencing.

View Article: PubMed Central - PubMed

Affiliation: Plant Science Department, McGill University, Macdonald Campus, Ste Anne de Bellevue, Quebec, Canada.

ABSTRACT
In animals and yeast, position effects have been well documented. In animals, the best example of this process is Position Effect Variegation (PEV) in Drosophila melanogaster. In PEV, when genes are moved into close proximity to constitutive heterochromatin, their expression can become unstable, resulting in variegated patches of gene expression. This process is regulated by a variety of proteins implicated in both chromatin remodeling and RNAi-based silencing. A similar phenomenon is observed when transgenes are inserted into heterochromatic regions in fission yeast. In contrast, there are few examples of position effects in plants, and there are no documented examples in either plants or animals for positions that are associated with the reversal of previously established silenced states. MuDR transposons in maize can be heritably silenced by a naturally occurring rearranged version of MuDR. This element, Muk, produces a long hairpin RNA molecule that can trigger DNA methylation and heritable silencing of one or many MuDR elements. In most cases, MuDR elements remain inactive even after Muk segregates away. Thus, Muk-induced silencing involves a directed and heritable change in gene activity in the absence of changes in DNA sequence. Using classical genetic analysis, we have identified an exceptional position at which MuDR element silencing is unstable. Muk effectively silences the MuDR element at this position. However, after Muk is segregated away, element activity is restored. This restoration is accompanied by a reversal of DNA methylation. To our knowledge, this is the first documented example of a position effect that is associated with the reversal of epigenetic silencing. This observation suggests that there are cis-acting sequences that alter the propensity of an epigenetically silenced gene to remain inactive. This raises the interesting possibility that an important feature of local chromatin environments may be the capacity to erase previously established epigenetic marks.

Show MeSH
Related in: MedlinePlus