Year-end Sale % OFF 
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.
Highlights
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 [1,2,3,4]
To investigate possible interactions between Programmed genome rearrangements (PGRs) and early gene silencing events, we applied indirect immunofluorescence labeling using antibodies against 5-methylcytosine (5meC), histone 3 trimethylated at lysine 9 (H3K9me3) and histone 3 trimethylated at lysine 27 (H3K27me3) to characterize the distribution of these modifications during early embryogenesis
This sequence is highly abundant within the germline and only localizes to two somatically retained chromosomes [6]. These analyses revealed that a majority of MNi, though not all, contain the Germ1 repeat, consistent with the interpretation that these micronuclei contain material destined for elimination from somatic lineages via PGR (Fig 1C and 1D, S1 Table)
Summary
Lampreys possess a fascinating genome biology wherein large portions of the genome, including large numbers of genes, are programmatically deleted during development. We present analyses and new techniques that significantly advance our understanding of the subcellular context of programmed rearrangements and interactions between programmed deletion and canonical DNA silencing mechanisms. We show that eliminated DNA exhibits a unique migration pattern during cell division, is packaged into discreet subcellular structures later in the cell cycle, and undergoes epigenetic silencing through DNA and histone methylation. These observations provide new insight into the mechanisms underlying programmed DNA loss and suggest a functional link between programmed DNA loss and other, more conserved gene silencing pathways
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
