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PNAS 103 (11): 4210-4215

Copyright © 2006 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor

Shreevrat Goenka*, and Mark Boothby*,{dagger},{ddagger}

*Department of Microbiology and Immunology and {dagger}Division of Rheumatology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2363

Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, and approved January 17, 2006

Received for publication August 11, 2005.

Abstract: The molecular mechanisms by which transcription is selectively activated and precisely controlled by signal transducer and activator of transcription (Stat) factors represent a central issue in cytokine-mediated cellular responses. Stat6 mediates responses to IL-4 and antagonizes Stat1 activated by IFN-{gamma}. We have discovered that Stat6 binds to collaborator of Stat6 (CoaSt6), a protein that lacks conventional coactivator motifs but contains three iterations of a domain found in the variant histone macroH2A. Although macroH2A participates in transcriptional silencing, the macro domains of CoaSt6 increased IL-4-induced gene expression. Moreover, CoaSt6 amplified Stat6-mediated but not IFN-{gamma}-induced gene expression, providing evidence of a selective coregulator of Stat-mediated gene transcription.

Key Words: coregulator • Stat1 • cytokine • macro domain

Author contributions: S.G. and M.B. designed research; S.G. performed research; S.G. contributed new reagents/analytic tools; S.G. and M.B. analyzed data; and S.G. and M.B. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. DQ372930).

{ddagger}To whom correspondence should be addressed. E-mail: mark.boothby{at}vanderbilt.edu

© 2006 by The National Academy of Sciences of the USA

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