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Molecular and Cellular Biology, April 2004, p. 3100-3111, Vol. 24, No. 8
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.8.3100-3111.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Drosophila Nipped-B Protein Supports Sister Chromatid Cohesion and Opposes the Stromalin/Scc3 Cohesion Factor To Facilitate Long-Range Activation of the cut Gene

Robert A. Rollins,1,{dagger} Maria Korom,2 Nathalie Aulner,2,{ddagger} Andrew Martens,2 and Dale Dorsett2*

Weill Graduate School of Medical Sciences, Cornell Medical College, New York, New York 10021,1 Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 631042

Received 29 August 2003/ Returned for modification 31 October 2003/ Accepted 14 January 2004

The Drosophila melanogaster Nipped-B protein facilitates transcriptional activation of the cut and Ultrabithorax genes by remote enhancers. Sequence homologues of Nipped-B, Scc2 of Saccharomyces cerevisiae, and Mis4 of Schizosaccharomyces pombe are required for sister chromatid cohesion during mitosis. The evolutionarily conserved Cohesin protein complex mediates sister chromatid cohesion, and Scc2 and Mis4 are needed for Cohesin to associate with chromosomes. Here, we show that Nipped-B is also required for sister chromatid cohesion but that, opposite to the effect of Nipped-B, the stromalin/Scc3 component of Cohesin inhibits long-range activation of cut. To explain these findings, we propose a model based on the chromatin domain boundary activities of Cohesin in which Nipped-B facilitates cut activation by alleviating Cohesin-mediated blocking of enhancer-promoter communication.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., Saint Louis, MO 63104. Phone: (314) 977-9218. Fax: (314) 977-9205. E-mail: dorsettd{at}slu.edu.

{dagger} Present address: Columbia Presbyterian College of Physicians and Surgeons, New York, NY 10032.

{ddagger} Present address: Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Molecular and Cellular Biology, April 2004, p. 3100-3111, Vol. 24, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.8.3100-3111.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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