Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor.
Growth factor independent-1 (Gfi1) is a zinc finger protein with a SNAG-transcriptional repressor domain. Ajuba is a LIM domain protein that shuttles between the cytoplasm and the nucleus. Ajuba functions as a co-repressor for synthetic Gfi1 SNAG-repressor domain-containing constructs, but a role for Ajuba co-repression of the cognate DNA bound Gfi1 protein has not been defined. Co-immunoprecipitation of synthetic and endogenous proteins and co-elution with gel filtration suggest that an endogenous Ajuba.Gfi1.HDAC multiprotein complex is possible. Active histone deacetylase activity co-immunoprecipitates with Ajuba or Gfi1, and both proteins depend upon histone deacetylases for full transcriptional repression activity. Ajuba LIM domains directly bind to Gfi1, but the association is not SNAG domain-dependent. ChIP analysis and reciprocal knockdown experiments suggest that Ajuba selectively functions as a co-repressor for Gfi1 autoregulation. The data suggest that Ajuba is utilized as a corepressor selectively on Gfi1 target genes.
Montoya-Durango
Diego E
DE
Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky 40202, USA.
Velu
Chinavenmeni S
CS
Kazanjian
Avedis
A
Rojas
Meghan E B
ME
Jay
Chris M
CM
Longmore
Gregory D
GD
Grimes
H Leighton
HL
D002460:Cell Line; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C485608:AJUBA protein, human; D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases