Kochendoerfer, A. M. | bioRxiv Science

bioRxiv2019

CENP-A drives asymmetric cell division and maintains stem identity

Centromeres, chromosomal loci essential for genome integrity, are epigenetically defined by CENP-A-containing chromatin. Recent studies suggest that parental CENP-A is asymmetrically distributed upon stem cell asymmetric division. However, a direct link between centromeres and stem cell identity has not been demonstrated. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres between G2-phase and prophase, requiring CYCLIN A. Intriguingly, chromosomes that will be inherited by GSCs incorporate more CENP-A and capture more spindle fibers at pro-metaphase. Furthermore, over-expression of CAL1 (Drosophila CENP-A assembly factor) causes GSC-like tumours, while over-expression of both CENP-A and CAL1 promotes stem cell self-renewal. Finally, once centromeres have been assembled in GSCs, continued CENP-A assembly is not required in differentiating cells outside of the niche and CAL1 becomes dispensable. According to our results CENP-A regulates stem cell identity/maintenance. Moreover, crucial centromere assembly occurs in the niche prior to oocyte meiosis.

cell biology↗

bioRxiv2019

RNA transcribed from heterochromatic simple-tandem repeats are required for male fertility and histone-protamine exchange in Drosophila melanogaster

Long arrays of simple, tandemly repeated DNA sequences (known as satellites) are enriched in centromeres1 and pericentromeric regions2, and contribute to chromosome segregation and other heterochromatin functions3,4. Surprisingly, satellite DNAs are expressed in many multicellular eukaryotes, and their aberrant transcription may contribute to carcinogenesis and cellular toxicity5-7. Satellite transcription and/or RNAs may also promote centromere and heterochromatin activities 8-12. However, we lack direct evidence that satellite DNA transcripts are required for normal cell or organismal functions. Here, we show that satellite RNAs derived from AAGAG tandem repeats are transcribed in many cell types throughout Drosophila melanogaster development, enriched in neuronal tissues and testes, localized within heterochromatic regions, and important for viability. Strikingly, we find that AAGAG transcripts are necessary for male fertility and are specifically required for normal histone-protamine exchange and sperm chromatin organization. Since AAGAG RNA-dependent events happen late in spermatogenesis when the transcripts are not detected, we speculate that AAGAG RNA functions in primary spermatocytes to prime post-meiosis steps in sperm maturation. In addition to demonstrating specific essential functions for AAGAG RNAs, comparisons between closely related Drosophila species suggest that satellite repeats and their transcription evolve quickly to generate new functions.

cell biology↗