title: Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR.
abstract: The evolutionarily conserved Hedgehog (Hh) signaling pathway is transduced by the Cubitus interruptus (Ci)/Gli family of transcription factors that exist in two distinct repressor (Ci(R)/Gli(R)) and activator (Ci(A)/Gli(A)) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which Ci(R)/Gli(R) properly represses target gene expression is poorly understood. Here, we used Drosophila melanogaster and zebrafish models to define a repressor function of Atrophin (Atro) in Hh signaling. Atro directly bound to Ci through its C terminus. The N terminus of Atro interacted with a histone deacetylase, Rpd3, to recruit it to a Ci-binding site at the decapentaplegic (dpp) locus and reduce dpp transcription through histone acetylation regulation. The repressor function of Atro in Hh signaling was dependent on Ci. Furthermore, Rerea, a homologue of Atro in zebrafish, repressed the expression of Hh-responsive genes. We propose that the Atro-Rpd3 complex plays a conserved role to function as a Ci(R) corepressor.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Chenyu
authors.initials: C
authors.lastname: Pan
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Lv
authors.forename: Wenqing
authors.initials: W
authors.lastname: Wu
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D056970:Co-Repressor Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D019143:Evolution, Molecular; D056426:Genetic Loci / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C092937:ci protein, Drosophila; C064196:dpp protein, Drosophila; C450826:gug protein, Drosophila; C513129:rerea protein, zebrafish; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1