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 Celljournal_title
Developmental cellauthors
Palladino J,Chavan A,Sposato A,Mason TD,Mellone BGdoi
10.1016/j.devcel.2020.01.005subject
Has Abstractpub_date
2020-02-10 00:00:00pages
379-394.e7issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(20)30006-Xjournal_volume
52pub_type
杂志文章abstract::The proper positioning of organs during development is essential, yet little is known about the regulation of this process in mammals. Using murine tooth development as a model, we have found that cell migration plays a central role in positioning of the organ primordium. By combining lineage tracing, genetic cell abl...
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