The modular mechanism of chromocenter formation in Drosophila.

Yukiko M Yamashita,Madhav Jagannathan,Ryan Cummings

doi:10.7554/elife.43938

Abstract

A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. Previously we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus (Jagannathan et al., 2018). Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a 'modular' network, where associations between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that associations between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.

Highlights

Satellite DNAs are abundant tandem repeats that are ubiquitously found at centromeric and pericentromeric heterochromatin of eukaryotic chromosomes
Our previous study demonstrated that the Drosophila D1 protein, which binds to the {AATAT}n satellite DNA, plays a critical role in bundling chromosomes into chromocenters, such that they are encapsulated within a single nucleus
Little if any {AATAT}n satellite DNA is present on 2nd chromosomes (Figure 1B), raising a question as to how these autosomes may be incorporated into chromocenters

Summary

Introduction

Satellite DNAs are abundant tandem repeats that are ubiquitously found at centromeric and pericentromeric heterochromatin of eukaryotic chromosomes. In a recent study using Drosophila and mouse cells as models, we have proposed a conserved function of satellite DNAs in maintaining the entire chromosomal complement in a single nucleus (Jagannathan et al, 2018). Our study indicated that pericentromeric satellite DNAs play a critical role in bundling multiple chromosomes, leading to the formation of ‘chromocenters’, cytological structures that have been recognized for ~100 years (Figure 1A) (Jones, 1970; Jost et al, 2012; Pardue and Gall, 1970). We have shown that Drosophila melanogaster D1 and the mouse HMGA1 bundle chromosomes by binding to their cognate satellite DNAs

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Conclusion