Cellular and Molecular Features of Developmentally Programmed Genome Rearrangement in a Vertebrate (Sea Lamprey: Petromyzon marinus)

Authors

Vladimir A. Timoshevskiy, University of KentuckyFollow
Joseph R. Herdy, University of KentuckyFollow
Melissa C. Keinath, University of KentuckyFollow
Jeramiah J. Smith, University of KentuckyFollow

Abstract

The sea lamprey (Petromyzon marinus) represents one of the few vertebrate species known to undergo large-scale programmatic elimination of genomic DNA over the course of its normal development. Programmed genome rearrangements (PGRs) result in the reproducible loss of ~20% of the genome from somatic cell lineages during early embryogenesis. Studies of PGR hold the potential to provide novel insights related to the maintenance of genome stability during the cell cycle and coordination between mechanisms responsible for the accurate distribution of chromosomes into daughter cells, yet little is known regarding the mechanistic basis or cellular context of PGR in this or any other vertebrate lineage. Here we identify epigenetic silencing events that are associated with the programmed elimination of DNA and describe the spatiotemporal dynamics of PGR during lamprey embryogenesis. In situ analyses reveal that the earliest DNA methylation (and to some extent H3K9 trimethylation) events are limited to specific extranuclear structures (micronuclei) containing eliminated DNA. During early embryogenesis a majority of micronuclei (~60%) show strong enrichment for repressive chromatin modifications (H3K9me3 and 5meC). These analyses also led to the discovery that eliminated DNA is packaged into chromatin that does not migrate with somatically retained chromosomes during anaphase, a condition that is superficially similar to lagging chromosomes observed in some cancer subtypes. Closer examination of “lagging” chromatin revealed distributions of repetitive elements, cytoskeletal contacts and chromatin contacts that provide new insights into the cellular mechanisms underlying the programmed loss of these segments. Our analyses provide additional perspective on the cellular and molecular context of PGR, identify new structures associated with elimination of DNA and reveal that PGR is completed over the course of several successive cell divisions.

Document Type

Article

Publication Date

6-24-2016

Notes/Citation Information

Published in PLOS Genetics, v. 12, no. 6, e1006103, p. 1-20.

© 2016 Timoshevskiy et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.pgen.1006103

Funding Information

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (https://www.nigms.nih.gov/Pages/default.aspx) under award number R01GM104123. This work was also supported by startup funds from the University of Kentucky, Department of Biology.

Repository Citation

Timoshevskiy, Vladimir A.; Herdy, Joseph R.; Keinath, Melissa C.; and Smith, Jeramiah J., "Cellular and Molecular Features of Developmentally Programmed Genome Rearrangement in a Vertebrate (Sea Lamprey: Petromyzon marinus)" (2016). Biology Faculty Publications. 112.
https://uknowledge.uky.edu/biology_facpub/112