Paramutation

In epigenetics, a paramutation is an interaction between two alleles at a single locus, whereby one allele induces a heritable change in the other allele. The change may be in the pattern of DNA methylation or histone modifications. The allele inducing the change is said to be paramutagenic, while the allele that has been epigenetically altered is termed paramutable. A paramutable allele may have altered levels of gene expression, which may continue in offspring which inherit that allele, even though the paramutagenic allele may no longer be present. Through proper breeding, paramutation can result in siblings that have the same genetic sequence, but with drastically different phenotypes. Though studied primarily in maize, paramutation has been described in a number of other systems, including animal systems like Drosophila melanogaster and mice. Despite its broad distribution, examples of this phenomenon are scarce and its mechanism is not fully understood. The first description of what would come to be called paramutation was given by William Bateson and Caroline Pellew in 1915, when they described "rogue" peas that always passed their "rogue" phenotype onto their progeny. However, the first formal description of paramutation was given by R.A. Brink at the University of Wisconsin–Madison in the 1950s, who did his work in maize (Zea mays). Brink noticed that specific weakly expressed alleles of the red1 (r1) locus in maize, which encodes a transcription factor that confers red pigment to corn kernels, can heritably change specific strongly expressed alleles to a weaker expression state. The weaker expression state adopted by the changed allele is heritable and can, in turn, change the expression state of other active alleles in a process termed secondary paramutation. Brink showed that the influence of the paramutagenic allele could persist for many generations. The alleles that cause heritable changes in the alleles they come into contact which are called paramutagenic, and the alleles modified by them are paramutable.

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Giovanna Ambrosini, Nicolas Jean Philippe Guex, Christian Iseli

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney,caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpre ...

BMC2024

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Daniele Tavernari, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta, Giovanni Ciriello

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Targeted search for scaling genes reveals matrix metalloproteinase 3 as a scaler of the dorsal-ventral pattern in Xenopus laevis embryos

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Targeted search for scaling genes reveals matrix metalloproteinase 3 as a scaler of the dorsal-ventral pattern in Xenopus laevis embryos