1. Atrophin–Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR
- Author
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Wenqing Wu, Jing Feng, Zhaocai Zhou, Yun Zhao, Chenyu Pan, Xiangdong Lv, Feng Liu, Lei Zhang, and Zhao Zhang
- Subjects
animal structures ,Repressor ,Histone Deacetylase 1 ,Biology ,Evolution, Molecular ,Histones ,Report ,Animals ,Drosophila Proteins ,Humans ,Hedgehog Proteins ,Hedgehog ,Transcription factor ,Zebrafish ,Research Articles ,Binding Sites ,Decapentaplegic ,Intracellular Signaling Peptides and Proteins ,Acetylation ,Cell Biology ,Zebrafish Proteins ,Molecular biology ,Hedgehog signaling pathway ,DNA-Binding Proteins ,Drosophila melanogaster ,Histone ,Genetic Loci ,biology.protein ,Histone deacetylase ,Co-Repressor Proteins ,Corepressor ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
Atrophin suppresses Hedgehog signaling by interacting with the transcriptional effector CiR and recruiting the histone deacetylase Rpd3 to the dpp locus to repress its transcription., 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 (CiR/GliR) and activator (CiA/GliA) forms. Aberrant activation of Hh signaling is associated with various human cancers, but the mechanism through which CiR/GliR 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 CiR corepressor.
- Published
- 2013