title: The Hippo effector Yorkie activates transcription by interacting with a histone methyltransferase complex through Ncoa6.
abstract: The Hippo signaling pathway regulates tissue growth in Drosophila through the transcriptional coactivator Yorkie (Yki). How Yki activates target gene transcription is poorly understood. Here, we identify Nuclear receptor coactivator 6 (Ncoa6), a subunit of the Trithorax-related (Trr) histone H3 lysine 4 (H3K4) methyltransferase complex, as a Yki-binding protein. Like Yki, Ncoa6 and Trr are functionally required for Hippo-mediated growth control and target gene expression. Strikingly, artificial tethering of Ncoa6 to Sd is sufficient to promote tissue growth and Yki target expression even in the absence of Yki, underscoring the importance of Yki-mediated recruitment of Ncoa6 in transcriptional activation. Consistent with the established role for the Trr complex in histone methylation, we show that Yki, Ncoa6, and Trr are required for normal H3K4 methylation at Hippo target genes. These findings shed light on Yki-mediated transcriptional regulation and uncover a potential link between chromatin modification and tissue growth.
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qing
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schozer
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Duojia
authors.initials: D
authors.lastname: Pan
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000091102:YAP-Signaling Proteins
chemical_list: D029721:Drosophila Proteins; D006657:Histones; C000599734:Ncoa6 protein, Drosophila; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C479519:TRR protein, Drosophila
keywords: D. melanogaster; Hippo signaling; developmental biology; growth control; histone methylation; stem cells; transcription factors