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Abstract
Centromeres are essential for accurate chromosome segregation and are
marked by CENP-A nucleosomes. Mis-targeted CENP-A chromatin has been shown to
seed centromeres at non-centromeric DNA. However, the requirements for such
de novo centromere formation and transmission in
vivo remain unknown. Here, we employ Drosophila
melanogaster and the LacI/lacO system to investigate the ability of
targeted de novo centromeres to assemble and be inherited
through development. De novo centromeres form efficiently at
six distinct genomic locations, which include actively transcribed chromatin and
heterochromatin, and cause widespread chromosomal instability. During tethering,
de novo centromeres sometimes prevail, causing the loss of
the endogenous centromere via DNA breaks and HP1-dependent epigenetic
inactivation. Transient induction of de novo centromeres and
chromosome healing in early embryogenesis show that, once established, these
centromeres can be maintained through development. Our results underpin the
ability of CENP-A chromatin to establish and sustain mitotic centromere function
in Drosophila . Centromere identity is thought to be specified epigenetically by
the
centromeric histone CENP-A, but whether targeted CENP-A chromatin can mediate
heritable de novo centromeres in vivo is
unknown. Palladino et al. show that multiple genomic locations
can acquire centromere activity and that these de novo
centromeres can be transmitted mitotically.