Seminar "Chromatin remodeling-mediated silencing of transposable elements"

Speaker:  Prof. Akihisa Osakabe
Graduate School of Science, Chiba University
Institute for Advanced Academic Research, Chiba University

Title: "Chromatin remodeling-mediated silencing of transposable elements"

Abstract: 

Transposable elements (TEs) constitute a substantial fraction of eukaryotic genomes and have profoundly influenced genome evolution. However, TE activation and mobilization can disrupt the expression of neighboring genes and compromise genome integrity, potentially leading to developmental abnormalities and disease. Consequently, TEs are generally recognized as potentially harmful genetic elements and are transcriptionally silenced through epigenetic mechanisms.

Genetic screening in Arabidopsis thaliana identified the chromatin remodeler DDM1 (Decrease in DNA Methylation 1) as a key factor required for maintaining repressive epigenetic modifications at TEs. The importance of this pathway is further underscored by the observation that loss-of-function mutations in the mammalian DDM1 ortholog, HELLS/LSH, are associated with Immunodeficiency, Centromeric instability, and Facial anomalies (ICF) syndrome, a disorder characterized by instability of pericentromeric genomic regions. These findings suggest that chromatin remodeling–mediated TE silencing represents an evolutionarily conserved mechanism in both plants and animals. Nevertheless, the molecular basis by which chromatin remodelers establish and maintain TE silencing, as well as the mechanisms underlying TE derepression upon loss of DDM1 function, have remained largely unresolved.

We combines biochemistry and structural biology using in vitro reconstituted chromatin with molecular genetics and genomics in Arabidopsis to elucidate the molecular mechanisms of TE silencing mediated by chromatin remodeling. Through these approaches, we have demonstrated that DDM1-dependent histone variant exchange on TEs is a critical determinant of TE regulation and have uncovered novel chromatin remodeling–based mechanisms that maintain repressive epigenetic states. In this seminar, I will present our recent findings and provide an overview of the molecular mechanisms by which chromatin remodeling contributes to transposon silencing.