PgmNr D147: The Drosophila Y chromosome acts as a heterochromatin sink and contributes to sex-specific aging.

Authors:
Emily Brown; Doris Bachtrog


Institutes
University of California, Berkeley, Berkeley, CA.


Keyword: heterochromatin

Abstract:

The Drosophila Y chromosome is gene poor and primarily consists of epigenetically silenced repetitive DNA, but nonetheless influences expression of thousands of genes genome-wide, possibly by sequestering heterochromatin machinery away from other positions in the genome.  To directly test the influence of the Y chromosome on heterochromatin genome-wide, we assayed the genomic distribution of histone marks associated with constitutive heterochromatin (H3K9me2 and H3K9me3) in flies with varying sex chromosome complements (XO, XY, and XYY males, and XX and XXY females).  We find that the number of Y chromosomes strongly influences the genome-wide enrichment patterns of repressive chromatin marks.  Highly repetitive regions are enriched for heterochromatin marks in wild-type males and females, and even more so in XO males.  In contrast, additional Y chromosomes in XXY females and XYY males dilute repressive marks away from normally silenced, repeat-rich regions, which is accompanied by a de-repression of Y-linked repeats.  This suggests that the Y chromosome can sequester heterochromatic factors, thus acting as a heterochromatin sink.

We also investigated the role of the Y chromosome and heterochromatin in sex-specific aging.  In most XY taxa, males have a shorter average lifespan than females, and accumulating evidence suggests that chromatin mis-regulation, and particularly loss of heterochromatin associated with aberrant expression of repetitive elements, contributes to organismal aging.  To investigate whether the Y chromosome's role as a heterochromatin sink could contribute to the shorter male lifespan, we collected lifepan and RNA-seq data from XY, XO, and XYY males, and XX and XXY females.  Our results suggest that the Y chromosome contributes to a shorter lifespan, as individuals with a Y chromosome, independent of sex, have a shorter lifespan.  Additionally, repetitive elements show greater mis-regulation during aging in individuals with a Y chromosome, especially Y-linked repeats, suggesting that the Y chromosome's influence on heterochromatin may contribute to a shorter average lifespan in males.