Abstract
A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi-AT-hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into 'chromocenters', a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serve a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells.
Highlights
Satellite DNA is AT-rich, non-coding, repetitive DNA that is abundant in centromeric and pericentromeric heterochromatin
Following siRNA-mediated knockdown of HMGA1, which led to near complete loss of HMGA1 protein, we observed chromocenter disruption in multiple mouse cell lines (Figure 1K–M, Figure 1—figure supplement 2J–L). These results suggest that D1 and HMGA1 have an orthologous function to organize pericentromeric satellite DNA into chromocenters
Pericentromeric heterochromatin has most often been studied and discussed in the context of how to maintain its heterochromatic, repressed nature (Nishibuchi and Dejardin, 2017), based on the assumption that the underlying sequences are mostly selfish, which have negative phenotypic consequences when derepressed in cells (Zeller and Gasser, 2017)
Summary
Satellite DNA is AT-rich, non-coding, repetitive DNA that is abundant in centromeric and pericentromeric heterochromatin. Cell Biology Chromosomes and Gene Expression eLife digest On Earth, life is divided into three domains The smallest of these domains includes all the creatures, from sunflowers to yeasts to humans, that have the genetic information within their cells encased in a structure known as the nucleus. It is well known that DNA is the blueprint for the building blocks of life, but most of the genetic information in a cell codes for nothing, and has unknown roles An example of such ‘junk DNA’ is pericentrometric satellite DNA, small repetitive sequences found on all chromosomes. New experiments by Jagannathan et al show that, in the nucleus of animal cells, certain DNA binding proteins make chromosomes huddle together by attaching to multiple pericentrometric satellite DNA sequences on different chromosomes If these proteins are removed from mice and fruit flies cells grown in the laboratory, the chromosomes cannot be clustered together. We suggest that satellite DNA function as a critical constituent of chromosomes and may serve an evolutionarily conserved role across eukaryotic species
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