The impact of chromatin on genome organisation, function and evolution

Introduction

Chromatin contributes to many important processes ensuring the proper functioning of eukaryotic cells. In addition, it shapes linear and spatial genome organisation, and specifies chromosomal regions including centromeres that play a key role in chromosome segregation. Chromatin-associated factors also fold the genome in 3D to enable the transfer of chromosomes during mitosis or to regulate gene expression.

Background

Chromatin composition is, however, not identical among eukaryotes. How differences in chromatin composition contribute to different linear and spatial genome organisations is largely unknown.

Research Aims

We aim to address these unknowns in three non-overlapping aims focusing on Lepidoptera and other insects as a model system.

1. Centromere Divergence
   First, we will investigate how the disruption of an essential chromatin-based epigenetic loop underlies a drastic case of centromere divergence. To this end, we will perform homology studies on centromere-specifying factors to correlate them with centromere profiles in representative insects that have convergently evolved a holocentric architecture (chromosome-wide centromeres) from monocentric ancestors (centromeres restricted to one chromosomal region).

2. Spatial Organisation of Mitotic Chromosomes
   Second, applying a combination of genomics, microscopy, and biophysical simulations in the holocentric moth Bombyx mori, we will test how the chromosome-wide distribution of centromeres affects the spatial organisation of mitotic chromosomes.

3. 3D Genome Organisation
   Third, using B. mori and exploiting extensive genomic datasets from related Lepidoptera, we will investigate how unprecedented features in 3D genome organisation, including a new chromatin compartment that we identified, affect genome function and organisation over evolutionary time.

Conclusion

With our proposal, we will reveal how changes in chromatin lead to reorganisation of essential genomic regions and shape the topology of chromosomes in 3D, and in turn how this spatial dimension influences genome structure across evolution.