Journal
JOURNAL OF CELL BIOLOGY
Volume 203, Issue 4, Pages 575-583Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201306012
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Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01010405, XDA01010406, XDA01010110]
- National Basic Research Program of China [2010CB912101, 2011CB943900, 2012CB945001, 2010CB945300]
- National Natural Science Foundation of China [31171414, 31171394, 31371492]
- Science and Technology Commission of Shanghai Municipality [11140900100]
- L. Zhang is the scholar of the Hundred Talents Program of the Chinese Academy of Sciences
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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.
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