The C. elegans dosage compensation complex mediates interphase X chromosome compaction.
BACKGROUND
Dosage 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 I(DC)) 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.


RESULTS
Using 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 I(DC). 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.


CONCLUSIONS
These results support the idea that condensin I(DC), 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.
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 Michigan.
Alyssa C
AC
Lau
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109 Michigan.
Kentaro
K
Nabeshima
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 Michigan.
Györgyi
G
Csankovszki
Caenorhabditis elegans; Chromatin; Chromosome condensation; Condensin; Dosage compensation; Epigenetics; Gene expression; Interphase chromosome