Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor.
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.
Goenka
Shreevrat
S
Department of Microbiology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
Boothby
Mark
M
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011064:Poly Adenosine Diphosphate Ribose / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D006657:Histones; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; C120756:macroH2A histone; D015847:Interleukin-4; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases