Non-B-form DNA structures mark centromeres

Abstract

Animal and plant centromeres are embedded in repetitive "satellite" DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-Bform conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequencespecific DNA binding proteins with DNA bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically non-essential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-Bform DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins.Our findings resolve the CENP-B paradox and provide a general basis for centromere specification.

Conservation, Divergence, and Functions of Centromeric Satellite DNA Families in the Bovidae

“…Recent studies on the architecture of centromeres have reported the presence of specific secondary structures such as DNA loops suggesting that active centromeric sequences were selected for their ability to form secondary structures, rather than for the nucleotide sequence itself (Aze et al. 2016; Kasinathan and Henikoff 2017). In fact, a bioinformatic analysis on the prediction of secondary structures showed that SAT1.723 can indeed form DNA loops and G-quadruplexes (data not shown; see Kejnovsky et al.…”