Work

Interchromosomal contacts between regulatory regions trigger stable transgenerational epigenetic inheritance in Drosophila

Year: 2024

Type: article

Abstract: Non-genetic information can be inherited across generations in a process known as transgenerational epigenetic inheritance (TEI). In Drosophila, hemizygosity of the Fab-7 regulatory element triggers inheritance of the histone mark H3K27me3 at a homologous locus on another chromosome, resulting in heritable epigenetic differences in eye color. Here, by mutating transcription factor binding sites within the Fab-7 element, we demonstrate the importance of the proteins pleiohomeotic and GAGA factor in the establishment and maintenance of TEI. We show that these proteins function by recruiting the polycomb repressive complex 2 and by mediating interchromosomal chromatin contacts between Fab-7 and its homologous locus, respectively. Using an in vivo synthetic biology system to induce them, we then show that chromatin contacts alone can establish TEI, providing a mechanism by which hemizygosity of one locus can establish epigenetic memory at another distant locus in trans through chromatin contacts.

Source: Molecular Cell

DOI: 10.1016/j.molcel.2024.11.021

Authors: Maximilian H. Fitz-James, Gonzalo Sabarís, Peter Sarkies, Frédéric Bantignies, Giacomo Cavalli

Institutions: Centre National de la Recherche Scientifique, Université de Montpellier, University of Oxford, Institut de Génétique Humaine

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $9,350