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Boulard Group

Epigenetic gene silencing in mammals

The Boulard group studies how epigenetic mechanisms govern genome function.

How do individual olfactory sensory neurons express a single receptor while silencing hundreds of paralogous genes?

Our lab explores how epigenetic mechanisms regulate gene expression in mammalian cells by partitioning the genome into active and silent domains. Our long-term goal is to decipher the regulatory logic arising from the interplay among the DNA sequence, its topology, local chromatin state, and transcription factors. 

Our research focus evolved from retrotransposon silencing and reversible glycosylation to the epigenetic determinants of neural diversity. We study one of the most remarkable instances of epigenetic gene regulation in mammals, namely olfactory receptor gene choice. This process restricts the expression of olfactory receptor genes to a single allele per neuron, selected in a largely random fashion from a vast repertoire numbering hundreds of paralogous genes. 

Our work revealed that the monogenic transcription of olfactory receptor genes is controlled by the epigenetic silencing of their super-enhancers. By resolving the factors and chromatin organisation that govern allelic exclusion at these enhancers, we aim to define general principles of enhancer choice across the genome.

Our major questions

We combine molecular genetics, single-cell genomics, biochemistry, and microscopy to investigate fundamental questions, including:

  • What is the chromatin mechanism that controls the monogenic transcription of olfactory receptor genes?
  • What is the role of heterochromatin in establishing neural identity?
  • What factors govern the plasticity and regeneration of olfactory sensory neurons?
Figure 1: Location of olfactory receptor genes and their super-enhancers on the mouse genome.
Figure 2: Individual mature olfactory sensory neurons express a single olfactory receptor gene. Left: low-dimensional representation of single-cell transcriptomes from the adult olfactory epithelium. Each dot represents a single cell. Neural cell types are colored; other cell types are shown in grey. Right: Heat map of olfactory receptor (OR) gene expression across individual mature olfactory sensory neurons; each neuron expresses a single OR gene.

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