Cell-Type Specific Variation in X-Chromosome Dosage Compensation in Drosophila

TL;DR

This study explores how X-chromosome gene expression is balanced in different cell types of male fruit flies, revealing that compensation varies significantly across tissues.

Contribution

The study reveals cell-type-specific variation in X-chromosome dosage compensation and suggests nonlinear regulation by RoX RNAs.

Findings

X-to-autosome expression ratios vary across cell types, showing anti-compensation, compensation, and overcompensation.

Anti-compensation is common in male reproductive tissues, while overcompensation is prevalent in neural cells.

RoX1 and RoX2 RNA levels correlate with compensation levels but do not fully explain the patterns observed.

Abstract

Male
Drosophila melanogaster
require dosage compensation to equalize X-linked gene expression with autosomal expression. Leveraging the single-nucleus Fly Cell Atlas (FCA) dataset, which includes 388,918 nuclei across diverse tissues, we investigated cell-type-specific patterns of X-chromosome dosage compensation. Our analysis identified a continuum of cell groups based on their X-to-autosome (X/A) expression ratios ranging from anti-compensated to effectively compensated and overcompensated. Anti-compensation was predominantly observed in male reproductive tissues, while overcompensation was prevalent in neural cells. The expression levels of the dosage compensation machinery's non-coding RNAs,
RoX1
and
RoX2
, correlated with compensation levels, but were insufficient to fully explain the observed patterns of compensation. These findings reveal the complexity of dosage compensation and suggest that its regulation by the
RoX
RNAs is nonlinear, implicating potential alternative mechanisms in certain cell types.

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