Non-canonical Drosophila X chromosome dosage compensation and repressive topologically associated domains

Hangnoh Lee,Brian Oliver

doi:10.1186/s13072-018-0232-y

Abstract

BackgroundIn animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in male Drosophila, there is a dosage compensation complex (MSL) that equilibrates X-linked gene expression with the autosomes. There are other potential contributions to dosage compensation. Hemizygous autosomal genes located in repressive chromatin domains are often derepressed. If this homolog-dependent repression occurs on the X, which has no pairing partner, then derepression could contribute to male dosage compensation.ResultsWe asked whether different chromatin states or topological associations correlate with X chromosome dosage compensation, especially in regions with little MSL occupancy. Our analyses demonstrated that male X chromosome genes that are located in repressive chromatin states are depleted of MSL occupancy; however, they show dosage compensation. The genes in these repressive regions were also less sensitive to knockdown of MSL components.ConclusionsOur results suggest that this non-canonical dosage compensation is due to the same transacting derepression that occurs on autosomes. This mechanism would facilitate immediate compensation during the evolution of sex chromosomes from autosomes. This mechanism is similar to that of C. elegans, where enhanced recruitment of X chromosomes to the nuclear lamina dampens X chromosome expression as part of the dosage compensation response in XX individuals.

Highlights

In animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes
X‐linked repressive Topologically associated domain (TAD) genes display low expression levels, but are dosage compensated in males To determine the overall structure of chromatin domains on the X, we used results from three previous studies that divided the genome into repressive versus nonrepressive chromatin domains/TADs and Lamina-associated domains (LAD) versus non-LADs
LAD and DamID (DNA adenine methyltransferase identification)-based chromatin occupancy information was from Kc cells [44, 45]

Summary

Introduction

In animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in male Drosophila, there is a dosage compensation complex (MSL) that equilibrates X-linked gene expression with the autosomes. Hemizygous autosomal genes located in repressive chromatin domains are often derepressed If this homolog-dependent repression occurs on the X, which has no pairing partner, derepression could contribute to male dosage compensation. In XY systems, males have what amounts to a heterozygous deletion of an entire chromosome, bearing ~ 20% of the genes in the case of Drosophila, with no impact on fitness. In such systems, compensation often rectifies gene dose effects as a way to maintain gene balance [3,4,5].

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