Abstract
BackgroundDosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. The DCC contains a subcomplex (condensin IDC) similar to the evolutionarily conserved condensin complexes which play fundamental roles in chromosome dynamics during mitosis and meiosis. Therefore, mechanisms related to mitotic chromosome condensation have been long hypothesized to mediate dosage compensation. However experimental evidence was lacking.ResultsUsing 3D FISH microscopy to measure the volumes of X and chromosome I territories and to measure distances between individual loci, we show that hermaphrodite worms deficient in DCC proteins have enlarged interphase X chromosomes when compared to wild type. By contrast, chromosome I is unaffected. Interestingly, hermaphrodite worms depleted of condensin I or II show no phenotype. Therefore X chromosome compaction is specific to condensin IDC. In addition, we show that SET-1, SET-4, and SIR-2.1, histone modifiers whose activity is regulated by the DCC, need to be present for the compaction of the X chromosome territory.ConclusionThese results support the idea that condensin IDC, and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction. Our results link condensin-mediated chromosome compaction, an activity connected to mitotic chromosome condensation, to chromosome-wide repression of gene expression in interphase.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-8935-7-31) contains supplementary material, which is available to authorized users.
Highlights
Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes
Dosage compensation mediates changes in X chromosome volumes To look for changes in chromosome packaging in dosage compensation we utilized chromosome-paint 3D fluorescent in situ hybridization (FISH) to measure the volumes of chromosome X and I territories in wild type and dosage compensation complex (DCC)-depleted hermaphrodite and male nuclei
In order to determine whether these chromatin modifications contribute to compaction of the X, we examined set-1(tm1821), set-4 (n4600), and sir-2.1(ok434) mutant worms
Summary
Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. In many species, such as humans, mice, flies, and worms, sex is determined by a chromosome-based method which entails a difference in sex chromosome number between heterogametic males (XY or XO) and homogametic females (XX). If left uncorrected this difference puts one sex at a disadvantage. Species have evolved a specialized gene regulatory mechanism to correct this imbalance, known as dosage compensation.
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