TY - JOUR
T1 - Atrophin controls developmental signaling pathways via interactions with Trithorax-like
AU - Yeung, Kelvin
AU - Boija, Ann
AU - Karlsson, Edvin
AU - Holmqvist, Per Henrik
AU - Tsatskis, Yonit
AU - Nisoli, Ilaria
AU - Yap, Damian
AU - Lorzadeh, Alireza
AU - Moksa, Michelle
AU - Hirst, Martin
AU - Aparicio, Samuel
AU - Fanto, Manolis
AU - Stenberg, Per
AU - Mannervik, Mattias
AU - McNeill, Helen
N1 - Publisher Copyright:
© Yeung et al.
PY - 2017/3/22
Y1 - 2017/3/22
N2 - Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro’s critical role in development and disease, relatively little is known about Atro’s binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways. We show that Atro regulates Dpp and Notch signaling in larval imaginal discs, at least partially via regulation of thickveins and fringe. In addition, bioinformatics analyses, sequential ChIP and coimmunoprecipitation experiments reveal that Atro interacts with the Drosophila GAGA Factor, Trithorax-like (Trl), and they bind to the same loci simultaneously. Phenotypic analyses of Trl and Atro clones suggest that Atro is required to modulate the transcription activation by Trl in larval imaginal discs. Taken together, these data indicate that Atro is a major Trl cofactor that functions to moderate developmental gene transcription.
AB - Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro’s critical role in development and disease, relatively little is known about Atro’s binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways. We show that Atro regulates Dpp and Notch signaling in larval imaginal discs, at least partially via regulation of thickveins and fringe. In addition, bioinformatics analyses, sequential ChIP and coimmunoprecipitation experiments reveal that Atro interacts with the Drosophila GAGA Factor, Trithorax-like (Trl), and they bind to the same loci simultaneously. Phenotypic analyses of Trl and Atro clones suggest that Atro is required to modulate the transcription activation by Trl in larval imaginal discs. Taken together, these data indicate that Atro is a major Trl cofactor that functions to moderate developmental gene transcription.
UR - http://www.scopus.com/inward/record.url?scp=85018919298&partnerID=8YFLogxK
U2 - 10.7554/eLife.23084
DO - 10.7554/eLife.23084
M3 - Article
C2 - 28327288
AN - SCOPUS:85018919298
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e23084
ER -