A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome.
In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites (recruitment elements on X) recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12-base-pair (bp) consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites (dependent on X) lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and noncompensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X-gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome.
Jans
Judith
J
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 97420, USA.
Gladden
John M
JM
Ralston
Edward J
EJ
Pickle
Catherine S
CS
Michel
Agnès H
AH
Pferdehirt
Rebecca R
RR
Eisen
Michael B
MB
Meyer
Barbara J
BJ
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D016384:Consensus Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004303:Dosage Compensation, Genetic / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049751:Genome, Helminth / Q000235:genetics / Q000502:physiology*; D008297:Male; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D000251:Adenosine Triphosphatases