Figure 1: Genome browser view of ChIP-seq data showing that chromatin proteins modified by O-GlcNAc are bound to the imprinted control regions (ICR) and to the differentially methylated regions (DMR) controlling gene expression of the Gnas imprinted cluster.
Figure 2: β-Gal staining of prospermatogonia, the non-dividing precursors to spermatogonial stem cells where de novo male-specific DNA methylation patterns are established.
The Boulard group integrates mouse genetics and genomic approaches to explore how cells silence parts of their genome.
Previous and current research
Our group studies how genetic information can be interpreted differently across cell types and time. We are particularly interested in understanding how mammalian cells regulate the availability of their genome by repressing some specific loci. For instance, female cells compensate for the presence of two X chromosomes by permanently inactivating one. Other examples of homologous genes showing opposite transcriptional states while being in the same nucleus include imprinted genes, a set of genes that are mono-allelically expressed in a parent-of-origin manner. Allele-specific epigenetic silencing is controlled by a chemical modification of the DNA called cytosine methylation. Sex-specific DNA methylation patterns are established in the parental germlines; their propagation during cell division makes them stable for the entire lifetime of an individual. In addition, cytosine methylation is also critical for host defence mechanisms by repressing parasitic genetic elements such as retrotransposons and exogenous retroviruses. Despite our detailed knowledge of the dynamics of genomic methylation patterns during the life cycle, the nature of the mechanism that represses methylated promoters has remained enigmatic.
While investigating this fundamental question, our group recently discovered that methylated retrotransposons are silenced by the glycosylation of associated proteins. We are currently studying further the biological output of chromatin glycosylation in the broader context of embryonic development and at systemic level.
Future projects and goals
We will continue to explore the molecular mechanisms of epigenetic gene regulation focusing on mono-allelic gene expression. To address these challenges in vivo, we will combine mouse genetics with genomic approaches and spatial transcriptomics.