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Molecular and Cellular Biology, August 2008, p. 4952-4962, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00219-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Regulation of Histone H4 Lys16 Acetylation by Predicted Alternative Secondary Structures in roX Noncoding RNAs{triangledown} ,{dagger}

Seung-Won Park,1,{ddagger} Mitzi I. Kuroda,2,3 and Yongkyu Park1*

Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103,1 Harvard-Partners Center for Genetics & Genomics, Brigham & Women's Hospital,2 Department of Genetics, Harvard Medical School, Boston, Massachusetts 021153

Received 10 February 2008/ Returned for modification 14 April 2008/ Accepted 29 May 2008

Despite differences in size and sequence, the two noncoding roX1 and roX2 RNAs are functionally redundant for dosage compensation of the Drosophila melanogaster male X chromosome. Consistent with functional conservation, we found that roX RNAs of distant Drosophila species could complement D. melanogaster roX mutants despite low homology. Deletion of a conserved predicted stem-loop structure in roX2, containing a short GUb (GUUNUACG box) in its 3' stem, resulted in a defect in histone H4K16 acetylation on the X chromosome in spite of apparently normal localization of the MSL complex. Two copies of the GUb sequence, newly termed the "roX box," were functionally redundant in roX2, as mutants in a single roX box had no phenotype, but double mutants showed reduced H4K16 acetylation. Interestingly, mutation of two of three roX boxes in the 3' end of roX1 RNA also reduced H4K16 acetylation. Finally, fusion of roX1 sequences containing a roX box restored function to a roX2 deletion RNA lacking its cognate roX box. These results support a model in which the functional redundancy between roX1 and roX2 RNAs is based, at least in part, on short GUUNUACG sequences that regulate the activity of the MSL complex.


* Corresponding author. Mailing address: Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103. Phone: (973) 972-2969. Fax: (973) 972-7489. E-mail: parky1{at}umdnj.edu

{triangledown} Published ahead of print on 9 June 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.


Molecular and Cellular Biology, August 2008, p. 4952-4962, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00219-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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