Identification of the gene transcription repressor domain of Gli3.
Gli transcription factors are downstream targets of the Hedgehog signaling pathway. Two of the three Gli proteins harbor gene transcription repressor function in the N-terminal half. We have analyzed the sequences and identified a potential repressor domain in Gli2 and Gli3 and have tested this experimentally. Overexpression studies confirm that the N-terminal parts harbor gene repression activity and we mapped the minimal repressor to residues 106 till 236 in Gli3. Unlike other mechanisms that inhibit Gli induced gene transcription, the repressor domain identified here does not utilize Histone deacetylases (HDACs) to achieve repression, as confirmed by HDAC inhibition studies and pull-down assays. This distinguishes the identified domain from other regulatory parts with negative influence on transcription.
Tsanev
Robert
R
Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.
Tiigimägi
Piret
P
Michelson
Piret
P
Metsis
Madis
M
Østerlund
Torben
T
Kogerman
Priit
P
D002460:Cell Line; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000074290:Zinc Finger Protein Gli3
C065683:GLI3 protein, human; D056572:Histone Deacetylase Inhibitors; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D000074290:Zinc Finger Protein Gli3; D006655:Histone Deacetylases