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. 2011 Jun;12(4):298-306.
doi: 10.2174/138920211795860099.

Paramutation: just a curiosity or fine tuning of gene expression in the next generation?

Roberto Pilu  1
Affiliations

Paramutation: just a curiosity or fine tuning of gene expression in the next generation?

Roberto Pilu. Curr Genomics. 2011 Jun.

Abstract

Gene silencing is associated with heritable changes in gene expression which occur without changes in DNA sequence. In eukaryotes these phenomena are common and control important processes, such as development, imprinting, viral and transposon sequence silencing, as well as transgene silencing. Among the epigenetic events, paramutation occurs when a silenced allele (named paramutagenic) is able to silence another allele (paramutable) in trans and this change is heritable. The silenced paramutable allele acquires paramutagenic capacity in the next generations. In the 1950s, Alexander Brink described for the first time the phenomenon of paramutation, occurring in maize at the colored1 (r1) gene, a complex locus (encoding myc-homologous transcription factors) that regulates the anthocyanin biosynthetic pathway. Since then, paramutation and paramutation-like interactions have been discovered in other plants and animals, suggesting that they may underlie important mechanisms for gene expression. The molecular bases of these phenomena are unknown. However in some cases, the event of paramutation has been correlated with changes in DNA methylation, chromatin structure and recently several studies suggest that RNA could play a fundamental role. This last consideration is greatly supported by genetic screening for mutants inhibiting paramutation, which allowed the identification of genes involved in RNA-directed transcriptional silencing, although it is possible that proteins are also required for paramutation.The meaning of paramutation in the life cycle and in evolution remains to be determined even though we might conjecture that this phenomenon could be involved in a fast heritability of favourable epigenetic states across generations in a non-Mendelian way.

Keywords: DNA methylation; Epigenetics; RNA-directed transcriptional silencing.; gene silencing; paramutation; repeated sequences.

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Figures

Fig. (1).
Fig. (1).
Scheme of classical paramutation phenomenon. Color intensity (from red = high expression to white = low expression) represents phenotypic expression of the A haplotype. A paramutable A allele undergoes spontaneous silencing inducing also paramutagenic activity (1). In the A’/A heterozygous (obtained by crossing individual carrying paramutagenic A’ allele with the paramutable A allele) the haplotypes segregating in the offspring are both A’ (because A’ has paramuted A) although the new A’ allele is less silenced than the original one (2). If the A’ paramutated allele is crossed with a paramutable allele a “secondary paramutation” is observed in the progeny (3). If a paramutated A’ allele is not exposed again in trans with the original A’ allele in few generations it will come back to the A paramutable phenotype (4). Crossing again the paramutated A’ allele with the strongest paramutagenic A’ this will induce in the progeny the reinforcing of the silencing in the A’’ haplotype (5).
Fig. (2).
Fig. (2).
Pedigree of the most famous cases of paramutation described in plants and animals. Paramutation in maize at the r1 locus (paramutable R-r and paramutagenic R-st alleles) involving the accumulation of anthocyanins in the maize seed (A) and in the whole plant in the case of b1 locus (paramutable B-I and paramutagenic B’ alleles) (B). Paramutation in tomato at the sulf locus (paramutable + and paramutagenic sulf alleles) causes chlorophyll-deficient phenotype (yellow color) (C). In mouse paramutation at the kit locus (paramutable + and paramutagenic Kittm1Alf alleles) confers white tail tips (D).
Fig. (3).
Fig. (3).
Spontaneous paramutation occurring at the pl1 locus in maize. A sector of yellow anther on the tassel (A) and one weakly colored seed on the ear (B) are shown in a B-I/B-I Pl-Rh/Pl-Rh plant (genotype conferring a strong anthocyanin accumulation on the whole plant).
Fig. (4).
Fig. (4).
Paramutation model in the b1 locus. In (A) is shown the spontaneous appearance of paramutagenic B’ from B-I, in (B) the B’ paramutation activity vs B-I and in (C) the four genes so far discovered involved in the RNAi machinery are indicated. The description of the model: (A) the B-I allele (red pigmented plant) is depicted by two boxes representing the seven tandem repeats and the b1 gene, the two boxes are united by hyphens indicating an active conformation of chromatin in this DNA region. Marked black arrows starting from b1 box represents the high transcription levels of B-I allele. An increase of CBBP protein level determines the binding of these proteins to the tandem repeats (1), in this step the RNAi machinery could also be involved (2). The CBBP proteins bonded to the tandem repeats in some way trigger the recruitment of the chromatin modification complex (3) which determines an hereditable silent conformation of chromatin structure (depicted by the sinusoid line between the two boxes) causing a strong decrease in b1 transcription levels (depicted by the thin black arrow starting from b1 box) and this new b1 epiallele named B’ (green pigmented plant) acquires paramutagenic capacity. (B) When a B-I allele is exposed in trans with a B’ paramutagenic allele (by crossing), an interaction (5) involving CBBP protein which binds the tandem repeats of B-I allele and perhaps a physical interaction between pairing genomic region on two chromosomes (indicated by the yellow arrow) and participation of RNAi machinery (4) cause the paramutation of B-I allele as described in A (7). In (C) are shown the proteins so far found involved in the maize paramutation: with the exception of CBBP are all implicated in the RNAi system: MOP1, MOP2, RMR1 and RMR6.
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