Function of Junk: Pericentromeric Satellite DNA in Chromosome Maintenance

Abstract

Satellite DNAs are simple tandem repeats that exist at centromeric and pericentromeric regions on eukaryotic chromosomes. Unlike the centromeric satellite DNA that comprises the vast majority of natural centromeres, function(s) for the much more abundant pericentromeric satellite repeats are poorly understood. In fact, the lack of coding potential allied with rapid divergence of repeat sequences across eukaryotes has led to their dismissal as "junk DNA" or "selfish parasites." Although implicated in various biological processes, a conserved function for pericentromeric satellite DNA remains unidentified. We have addressed the role of satellite DNA through studying chromocenters, a cytological aggregation of pericentromeric satellite DNA from multiple chromosomes into DNA-dense nuclear foci. We have shown that multivalent satellite DNA-binding proteins cross-link pericentromeric satellite DNA on chromosomes into chromocenters. Disruption of chromocenters results in the formation of micronuclei, which arise by budding off the nucleus during interphase. We propose a model that satellite DNAs are critical chromosome elements that are recognized by satellite DNA-binding proteins and incorporated into chromocenters. We suggest that chromocenters function to preserve the entire chromosomal complement in a single nucleus, a fundamental and unquestioned feature of eukaryotic genomes. We speculate that the rapid divergence of satellite DNA sequences between closely related species results in discordant chromocenter function and may underlie speciation and hybrid incompatibility.

DICER regulates the expression of major satellite repeat transcripts and meiotic chromosome segregation during spermatogenesis

“…The mechanisms involved in the regulation of MSR transcription have remained poorly characterized. However, current evidence supports the functional significance of MSR transcription for example in the epigenetic silencing of pericentric heterochromatin and chromocenter formation ( 34 , 35 , 38–41 ).…”

“…Centromeric and pericentric regions have an important role in chromosome segregation during cell division, and transcription of these regions has been implicated to have a functional role in this process ( 19 , 20 , 38 ). Therefore, we wanted to explore if misregulation of pericentric heterochromatic MSR expression in meiotic spermatocytes in the absence of DICER affects meiotic chromosome segregation.…”

“…miRNA processing). Nonetheless, given the importance of pericentric and centromeric heterochromatin in chromatin organization and chromosome segregation ( 19 , 20 , 24–28 , 38 ), it is a plausible hypothesis that the defects in the control of MSR transcript expression and processing contribute to the meiotic phenotype of Dicer1 cKO mice.…”

Genomic Tackling of Human Satellite DNA: Breaking Barriers through Time

“…The name satellite DNA (satDNA) was here to stay [ 12 ] and has been used ever since as a broader term for tandem repeats [ 13 ]. Fundamentally, satDNAs make up the eukaryotic centromeric and pericentromeric genomic regions [ 14 ], even though they can also be located at subtelomeric sites or even at interstitial regions [ 15 , 16 , 17 ]. SatDNA sequences can be distinguished by a multitude of dissimilar features, like nucleotide sequence composition, complexity, and abundance, although their major shared characteristics cannot be dismissed: the capacity to form heterochromatic regions and the intrinsic propensity to form long tandemly organized arrays [ 17 ].…”

Bundling up DNA

“…This suggests that during interphase, the chromocenters keep the genome within the nucleus by gathering pericentromeric DNA from different chromosomes. Evolution would select for satellite DNA that binds a bundling protein, but not for the satellite sequence itself, which can rapidly diverge between species ( Jagannathan and Yamashita, 2018 ; Jagannathan et al, 2018 ).…”