Targeted De Novo Centromere Formation in Drosophila Reveals Plasticity and Maintenance Potential of CENP-A Chromatin.

Abstract:

:Centromeres are essential for accurate chromosome segregation and are marked by centromere protein A (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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Palladino J,Chavan A,Sposato A,Mason TD,Mellone BG

doi

10.1016/j.devcel.2020.01.005

subject

Has Abstract

pub_date

2020-02-10 00:00:00

pages

379-394.e7

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(20)30006-X

journal_volume

52

pub_type

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