Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2003]-

Heterochromatin*/metabolism ; Heterochromatin*/genetics ; Proteome*/metabolism ; Drosophila Proteins*/metabolism ; Drosophila Proteins*/genetics ; DNA, Satellite*/metabolism ; DNA, Satellite*/genetics ; DNA Transposable Elements*/genetics; Animals ; Female ; Male ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/embryology ; Ovary/metabolism ; Testis/metabolism ; RNA, Small Interfering/metabolism ; RNA, Small Interfering/genetics

Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized. Here, we use 2 satellite DNA-binding proteins, D1 and Prod, as baits to characterize the chromocenter-associated proteome in Drosophila embryos, ovaries, and testes through quantitative mass spectrometry. We identify D1- and Prod-associated proteins, including known heterochromatin proteins as well as proteins previously unlinked to satellite DNA or chromocenters, thereby laying the foundation for a comprehensive understanding of cellular functions enabled by satellite DNA repeats and their associated proteins. Interestingly, we find that multiple components of the transposon-silencing piRNA pathway are associated with D1 and Prod in embryos. Using genetics, transcriptomics, and small RNA profiling, we show that flies lacking D1 during embryogenesis exhibit transposon expression and gonadal atrophy as adults. We further demonstrate that this gonadal atrophy can be rescued by mutating the checkpoint kinase, Chk2, which mediates germ cell arrest in response to transposon mobilization. Thus, we reveal that a satellite DNA-binding protein functions during embryogenesis to silence transposons, in a manner that is heritable across later stages of development.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2025 Chavan 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.)

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0 (Heterochromatin)
0 (Proteome)
0 (Drosophila Proteins)
0 (DNA, Satellite)
0 (DNA Transposable Elements)
0 (RNA, Small Interfering)

Date Created: 20250115 Date Completed: 20250115 Latest Revision: 20250129

20250129

PMC11734925

10.1371/journal.pbio.3002984

39813297