Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR

Zhao Zhang, Jing Feng, Chenyu Pan, Xiangdong Lv, Wenqing Wu, Zhaocai Zhou, Feng Liu, Lei Zhang, Yun Zhao

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
JournalJournal of Cell Biology
Volume203
Issue number4
DOIs
StatePublished - Nov 25 2013
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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