Keeping a Genomic Jungle in Check; How Eukaryotic Cells Regulate the Positive Feedback of Heterochromatin Expansion
Summary
Eukaryotic genomes contain many repetitive sequences that, without constant repression, can induce genomic
instability via rogue transcription, recombination, and transposition. Repression of these sequences occurs through constitu-
tive heterochromatin, a condensed phase consisting of H3K9me2/3-marked nucleosomes bound to DNA. Interestingly, whilst
heterochromatin nucleation in sequence-dependent, its propagation is both sequence-independent and self-reinforced via
positive-feedback loops. As the abnormal repression of genes can have large implications for cellular fitness, it is important
that these mechanisms be spatiotemporally regulated. How this is mediated is, however, not fully known. In this review, we
examine recent findings on the nucleation, spreading and regulation of constitutive heterochromatin. We then use this infor-
mation to form models explaining the regulation of constitutive heterochromatin, to speculate on topics for future research.
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