Genetics. Published Articles Ahead of Print: May 16, 2007, Copyright © 2007
doi:10.1534/genetics.107.071571


A more recent version of this article appeared on July 1, 2007.


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Regional control of chromatin organization by noncoding roX RNAs and the NURF remodeling complex in Drosophila melanogaster

1 Children's Hospital, Boston
2 Brigham and Women's Hospital
3 University of Birmingham

* To whom correspondence should be addressed. E-mail: mkuroda{at}genetics.med.harvard.edu.

Submitted on January 31, 2007
Revised on March 12, 2007
Accepted on 22 April 2007


Abstract

Dosage compensation in Drosophila is mediated by a histone-modifying complex that upregulates transcription of genes on the single male X chromosome. The male-specific lethal (MSL) complex contains at least 5 proteins and two non-coding roX (RNA on X) RNAs. The mechanism by which the MSL complex targets the X chromosome is not understood. One model is that the complex spreads in cis from a limited number of initial sites such as roX genes. Here we use a sensitized system to test the function of roX genes on the X chromosome. In mutants that lack the NURF nucleosome remodeling complex, the male polytene X chromosome is severely distorted, appearing decondensed. This aberrant morphology is dependent on the MSL complex. Strikingly, roX mutations suppress the Nurf mutant phenotype regionally on the male X chromosome. Furthermore, a roX transgene induces disruption of local flanking autosomal chromatin in Nurf mutants. Taken together, these results demonstrate the potent capability of roX genes to set up a local chromatin domain in cis, providing strong evidence for the spreading mechanism. In addition to antagonistic functions at the level of chromosome morphology, we also find that NURF complex and MSL proteins have opposing effects on roX RNA transcription. Together, these results demonstrate the importance of a local balance between modifying activities that promote and antagonize chromatin compaction within defined chromatin domains in higher organisms.

Key Words: Drosophila, NURF, chromatin, dosage compensation, noncoding RNAs




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