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Chromatin conversations: mechanisms and implications of paramutation

Key Points

  • Paramutation involves trans-interactions that lead to heritable changes in a phenotype, the most frequent of which is gene expression.

  • Paramutation can occur between two alleles of the same gene, or two transgenes, or one transgene and an endogenous gene.

  • Paramutation-like phenomena have been observed in several species, including fungi, plants and animals.

  • In the paramutation examples that involve changes in gene expression that have been tested, transcription is altered.

  • Differences in chromatin, such as DNA methylation and/or nuclease hypersensitivity, correlate with paramutation.

  • Tandem repeats are required for paramutation in several systems.

  • Mutations that prevent paramutation also affect transposon and transgene silencing.

  • Multiple mechanisms are likely to be involved in paramutation.

  • Two non-mutually exclusive models for trans-interactions are pairing and trans-acting RNA signals.

Abstract

Paramutation is a widespread epigenetic phenomenon that was first described in pea and then extensively studied in maize, whereby combining two specific alleles results in a heritable change in the expression of one of the alleles. Far from being restricted to endogenous plant genes, paramutation-like interactions have been described in several kingdoms, in which they can occur between homologous transgenes or between transgenes and homologous endogenous genes at allelic or non-allelic positions. In this review, we discuss potential mechanisms underlying paramutation, compare paramutation to several other trans-sensing phenomena, and speculate on the potential roles and evolutionary implications of these intriguing homology-sensing mechanisms.

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Figure 1: Models for paramutation.

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Related links

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DATABASES

Entrez Gene

Air

Rasgrf1

Tsix

U2af1-rs1

Xist

TAIR

ago1

cmt3

ddm1

kyp

met1

mom1

PAI

PAI2

FURTHER INFORMATION

The Plant Chromatin Database

Vicki Chandler's web page

Maike Stam's web page

Glossary

MENDEL'S FIRST LAW

This states that in the process of the formation of the gametes the allelic pairs separate, one going to each gamete, and that each gene remains completely uninfluenced by the other.

EPIGENETICS

Describes a heritable effect on chromosome or gene function that is not accompanied by a change in DNA sequence. It is accompanied by modifications of chromatin or DNA.

EPIALLELES

An epigenetic variant of an allele. The activity of an epiallele is dependent on epigenetic modifications (for example, histone deacetylation and cytosine methylation) and not on nucleotide changes.

NUCLEASE HYPERSENSITIVITY

The presence of chromosomal sites that are highly accessible to cleavage by nucleases such as deoxyribonuclease I (DNAseI). Such sites indicate the binding of proteins to specific sites, and tend to be associated with transcriptional activity of the nearby gene.

PENETRANCE

The frequency with which individuals that carry a given gene or epiallele will show the manifestations associated with the gene or epiallele.

MUTATOR

A specific class of maize transposable element. A transposable element is genetic material that is capable of changing its location in the genome of an organism.

HERITABILITY

Classically defined as the proportion of the variation in a given characteristic or state that can be attributed to genetic factors. In the context of epigenetics, it means that the epigenetic state is transmitted to progeny.

PERICARP

The ovary wall that forms the seed coat.

VARIEGATION PROPERTIES

The object showing variegation properties can show a variety of phenotypes within somatic sectors, usually reflecting the clonal patterns of cell division in the tissue. Typically, these involve easily visualized differences in pigment.

INTERSTITIAL HETEROCHROMATIN

Heterochromatic regions that are situated in the body of a chromosome (regions other than centromeric and telomeric heterochromatin). The term heterochromatin is widely used for the densely-staining regions of the nucleus that generally contain condensed, transcriptionally inactive regions of the genome.

LAC OPERATOR

A DNA regulatory element that is derived from the E. coli lac operon that interacts with the lacI repressor.

TET OPERATOR

A control element of the tetracycline-resistance operon from Escherichia coli. The tet operator interacts with the tet repressor.

SYNAPSIS

The pairing of homologous chromosomes along their length; synapsis usually occurs during prophase I of meiosis, but it can also occur in somatic cells of some organisms.

spt::Ac TRANSGENE

A transgene that carries the streptomycin phosphotransferase (spt) gene. It carries the maize transposable element Activator (Ac) that is inserted into the 5′ untranslated leader of the spt gene.

POLYCOMB-GROUP PROTEINS

A class of proteins — originally described in Drosophila melanogaster — that maintain stable and heritable repression of a number of genes, including the homeotic genes, with which they are associated.

GENE CONVERSION

A specific type of recombination in which the sequence of one DNA strand is used to alter the sequence of the other, resulting in non-reciprocal genetic exchange.

ALLOTETRAPLOID

A polyploid organism that is established from hybridization of two different species. This organism carries four complete sets of chromosomes, two derived from each parental species.

COMPLEX

A measured phenotype, such as disease status or a quantitative character, which is influenced by many environmental and genetic factors, and potentially by interactions within and between them.

VARIABLE NUMBER OF TANDEM REPEAT (VNTR) LOCUS

A locus that contains a variable number of short tandemly repeated DNA sequences that vary in length and are highly polymorphic.

HETEROSIS

The greater fitness of a hybrid individual carrying different alleles of genes relative to either of the two corresponding homozygous parents.

MICROSYNTENY

Collinearity in the order of genes and intervening DNA sequences in homologous chromosomal regions of two (sub)species.

OVERDOMINANCE

Describes the greater phenotypic expression seen in the heterozygote compared to that of either homozygote.

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Chandler, V., Stam, M. Chromatin conversations: mechanisms and implications of paramutation. Nat Rev Genet 5, 532–544 (2004). https://doi.org/10.1038/nrg1378

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