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PNAS 102 (16): 5749-5754

Copyright © 2005 by the National Academy of Sciences.


DEVELOPMENTAL BIOLOGY

Reverse recruitment: The Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation

Balaraj B. Menon *, Nayan J. Sarma *, Satish Pasula *, Stephen J. Deminoff * {dagger}, Kristine A. Willis {ddagger}, Kellie E. Barbara *, Brenda Andrews {ddagger}, and George M. Santangelo *, §

*Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406; and {ddagger}Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada M5S 1A8

Communicated by Michael S. Levine, University of California, Berkeley, CA, March 4, 2005

Received for publication January 10, 2005.

Abstract: The recruitment model for gene activation presumes that DNA is a platform on which the requisite components of the transcriptional machinery are assembled. In contrast to this idea, we show here that Rap1/Gcr1/Gcr2 transcriptional activation in yeast cells occurs through a large anchored protein platform, the Nup84 nuclear pore subcomplex. Surprisingly, Nup84 and associated subcomplex components activate transcription themselves in vivo when fused to a heterologous DNA-binding domain. The Rap1 coactivators Gcr1 and Gcr2 form an important bridge between the yeast nuclear pore complex and the transcriptional machinery. Nucleoporin activation may be a widespread eukaryotic phenomenon, because it was first detected as a consequence of oncogenic rearrangements in acute myeloid leukemia and related syndromes in humans. These chromosomal translocations fuse a homeobox DNA-binding domain to the human homolog (hNup98) of a transcriptionally active component of the yeast Nup84 subcomplex. We conclude that Rap1 target genes are activated by moving to contact compartmentalized nuclear assemblages, rather than through recruitment of the requisite factors to chromatin by means of diffusion. We term this previously undescribed mechanism "reverse recruitment" and discuss the possibility that it is a central feature of eukaryotic gene regulation. Reverse recruitment stipulates that activators work by bringing the DNA to an nuclear pore complex-tethered platform of assembled transcriptional machine components.

Key Words: chromatin boundaries • leukemia • silencing • synthetic genetic array • gene regulation


Freely available online through the PNAS open access option.

Abbreviations: NPC, nuclear pore complex; SGA, synthetic genetic array.

{dagger} Present address: Department of Molecular Genetics, Ohio State University, Columbus, OH 43210.

§ To whom correspondence should be addressed at: Department of Biological Sciences, University of Southern Mississippi, 118 College Drive, Hattiesburg, MS 39406. E-mail: george.santangelo{at}usm.edu.

© 2005 by The National Academy of Sciences of the USA


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