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M608741200v1
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Papers In Press, published online ahead of print December 6, 2006
J. Biol. Chem, 10.1074/jbc.M608741200
Submitted on September 11, 2006
Revised on December 4, 2006
Accepted on December 6, 2006

Actively transcribed GAL genes can be physically linked to the nuclear pore by the SAGA chromatin modifying complex

Roopa Luthra, Shana C. Kerr, Michelle T. Harreman, Luciano H. Apponi, Milo B. Fasken, Suneela Ramineni, Shyam Chaurasia, Sandro R. Valentini, and Anita H. Corbett

Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

Corresponding Author: acorbe2{at}emory.edu

Recent work has demonstrated that some actively transcribed genes closely associate with nuclear pore complexes (NPC) at the nuclear periphery. The Saccharomyces cerevisiae Mlp1 and Mlp2 proteins are components of the inner nuclear basket of the nuclear pore that mediate interactions with these active genes. To investigate the physical link between the NPC and active loci, we identified proteins that interact with the C-terminal globular domain of Mlp1 by tandem affinity purification (TAP) coupled with mass spectrometry. This analysis led to the identification of several components of the Spt-Ada-Gcn5-Acetyl-transferase (SAGA) histone acetyltransferase complex, Gcn5, Ada2, and Spt7. We utilized co-immunoprecipitation and in vitro binding assays to confirm the interaction between the Mlp proteins and SAGA components. Chromatin immunoprecipitation (ChIP) experiments revealed that Mlp1 and SAGA components associate with the same region of the GAL promoters. Critically, this Mlp-promoter interaction depends on the integrity of the SAGA complex. These results identify a physical association between SAGA and the NPC, and support previous results which relied upon visualization of GAL loci at the nuclear periphery by microscopy [Cabal, G. G., et al. (2006) Nature. 441, 770-3]. We propose that a physical interaction between nuclear pore components and the SAGA complex can link the actively transcribed GAL genes to the nuclear pore.


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C. R. Brown, C. J. Kennedy, V. A. Delmar, D. J. Forbes, and P. A. Silver
Global histone acetylation induces functional genomic reorganization at mammalian nuclear pore complexes
Genes & Dev., March 1, 2008; 22(5): 627 - 639.
[Abstract] [Full Text] [PDF]




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