Centromere function in asymmetric cell division in Drosophila female and male germline stem cells

Abstract

The centromere is the constricted chromosomal region required for the correct separation of the genetic material at cell division. The kinetochore protein complex assembles at the centromere and captures microtubules emanating from the centrosome to orchestrate chromosome segregation in mitosis and meiosis. Asymmetric cell division (ACD) is a special type of mitosis that generates two daughter cells with different fates. Epigenetic mechanisms operating at the centromere have been proposed to contribute to ACD. Recent studies have shown that an asymmetric distribution of CENP-A—the centromere-specific histone H3 variant—between sister chromatids can bias chromosome segregation in ACD. In stem cells, this leads to non-random sister chromatid segregation, which can affect cell fate. These findings support the ‘silent sister' hypothesis, according to which the mechanisms of ACD are epigenetically regulated through centromeres. Here, we review the recent data implicating centromeres in ACDs and cell fate in Drosophila melanogaster female and male germline stem cells.

Old and newly synthesized histones are asymmetrically distributed in Drosophila intestinal stem cell divisions

“…It will be intriguing to explore in the future what histone modifications are associated with old versus new histones. Furthermore, asymmetric sister centromere in recognizing sister chromatids during ACD has also been reported in Drosophila male GSCs (Ranjan et al, 2019;Kochendoerfer et al, 2021Kochendoerfer et al, , 2023) and female GSCs Dattoli et al, 2020;Carty et al, 2021;Kochendoerfer et al, 2021). Asymmetric inheritance of old versus new centromere-specific histone variant CENP-A/CID has also been reported in the Drosophila ISCs (Garcia Del Arco et al, 2018).…”

Centromere proteins are asymmetrically distributed between newly divided germline stem and daughter cells and maintain a balanced niche in Drosophila males

“…In Drosophila males, the GSC niche, the specific microenvironment in which GSCs are present in an undifferentiated and self-renewable state, is located at the apical end of each testis. Depending on the fly line, between 6 and 15 GSCs are positioned surrounding a cluster of nondividing stromal cells called the hub ( Kochendoerfer et al. , 2021 ).…”

“…, 2020 ). Based on these observations, a mitotic drive model has been proposed as a mechanism that contributes to ACD via centromere strength ( Kochendoerfer et al. , 2021 ; Ranjan and Chen, 2022 ).…”

CENP-A: A Histone H3 Variant with Key Roles in Centromere Architecture in Healthy and Diseased States

“…In Drosophila, intestinal stem cells preferentially retain pre-existing CENP-A during asymmetric divisions, when one daughter cell differentiates and the other daughter cell maintains stemness (García del Arco et al 2018), suggesting that CENP-A nucleosomes may epigenetically mark stem cell identity in this system. Indeed, asymmetric mitosis depends on the asymmetric loading of CENP-A loading on sister chromatids in both male (Ranjan et al 2019) and female (Dattoli et al 2020;Carty et al 2021) Drosophila germline (reviewed in (Kochendoerfer et al 2021)). This asymmetry in CENP-A is also associated with asymmetry in CENP-C, CAL1 (HJURP-like chaperone for Drosophila CENP-A), and NDC80.…”