Dear Editor, The highly conserved polycomb group （PcG） proteins were initially identified in Drosophila to maintain repression state of the transcription of homeotic genes, which is critical for animal development ...Dear Editor, The highly conserved polycomb group （PcG） proteins were initially identified in Drosophila to maintain repression state of the transcription of homeotic genes, which is critical for animal development control （Sawarkar and Paro, 2010）. Polycomb repressive complexes 1 （PRC1） and 2 （PRC2） are two important multi-protein complexes of PcG proteins regulating target gene expression. In Drosophila, PRC2 is composed of Enhancer of zeste （E（z））, Suppressor of zeste 12 （5u（z）I2）, Extra sex combs （esc）, and Chromatin assembly factor 1 subunit （Cafl）. E（z） is the catalytic subunit for H3K27me2/3, while both Su（z）l_2 and Esc are required for the proper catalytic activity in vivo （Helin and Morey, 2010）. PRC1 contains a core of four proteins： Polycomb （Pc）, Polyhomeotic （Ph）, Sex combs extra （Sce）, and Posterior sex combs （Psc）. Through its chromodomain, Pc can specifically recognize H3K27me3, and recruit other components to selected chromatin sites （Beisel and Paro, 2011）, although H3K27me3-independent recruitment of PRC1 has also been reported. PRC1 can repress its targets by either catalyzing H2A mono-ubiquitination （Wang et al., 2004） or inducing local chromatin condensation （Eskeland et al., 2010）.展开更多
The Hedgehog （Hh） signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus （Ci）. Ye...The Hedgehog （Hh） signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus （Ci）. Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile （1） homeotic （Fsh）, a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra （Sce）, and Polycomb （Pc）. Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engraited （En）, a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.展开更多
基金Supplementary material is available at Journal of Molecular Cell Biology online. We are grateful to Drs Jeffrey A. Simon （University of Minnesota, USA）, Jurg Muller （Max Planck Institute of Biochemistry, Germany）, Rongwen Xi （National Institute of Biological Science, Beijing, China）, Sharon E. Bickel （Dartmouth College, USA）, Renjie Jiao （Chinese Academy of Sciences, Beijing, China）, DSHB, VDRC, NIG, and the Bloomington Stock Center for fly stocks and reagents. We also thank Dr Jin-Qiu Zhou （Chinese Academy of Sciences, Shanghai, China） for discussions and comments on the manuscript. This work was supported by grants from the National Natural Science Foundation of China （31630047, 31671453, and 31771610）, the National Key Research and Development Program of China （2017YFA0503600）, the ＇Strategic Priority Research Program＇ of the Chinese Academy of Sciences （XDB19020100）, the Program of Shanghai Academic/Fechnology Research Leader （17XD1404100）, the International Partnership Program of Chinese Academy of Sciences （153D31KYSB20160137）, and the ＇Cross and Cooperation in Science and Technology Innovation Team＇ Project of the Chinese Academy of Sciences （173176001000163307）.
文摘Dear Editor, The highly conserved polycomb group （PcG） proteins were initially identified in Drosophila to maintain repression state of the transcription of homeotic genes, which is critical for animal development control （Sawarkar and Paro, 2010）. Polycomb repressive complexes 1 （PRC1） and 2 （PRC2） are two important multi-protein complexes of PcG proteins regulating target gene expression. In Drosophila, PRC2 is composed of Enhancer of zeste （E（z））, Suppressor of zeste 12 （5u（z）I2）, Extra sex combs （esc）, and Chromatin assembly factor 1 subunit （Cafl）. E（z） is the catalytic subunit for H3K27me2/3, while both Su（z）l_2 and Esc are required for the proper catalytic activity in vivo （Helin and Morey, 2010）. PRC1 contains a core of four proteins： Polycomb （Pc）, Polyhomeotic （Ph）, Sex combs extra （Sce）, and Posterior sex combs （Psc）. Through its chromodomain, Pc can specifically recognize H3K27me3, and recruit other components to selected chromatin sites （Beisel and Paro, 2011）, although H3K27me3-independent recruitment of PRC1 has also been reported. PRC1 can repress its targets by either catalyzing H2A mono-ubiquitination （Wang et al., 2004） or inducing local chromatin condensation （Eskeland et al., 2010）.
基金This study was supported by grants from the National Natural Science Foundation of China （31630047, 31671453, 31771610）, the National Key Research and Development Program of China （2017YFA0503600）, and the ＇Strategic Priority Research Program＇ of the Chinese Academy of Sciences （XDB19020100） and was sponsored by the Program of Shanghai Academic/Technology Research Leader （17XD1404100）, the International Partnership Program of Chinese Academy of Sciences （153D31KYSB20160137）, and the ＇Cross and Cooperation in Science and Technology Innovation Team＇ Project of the Chinese Academy of Sciences （173176001000163307）.
文摘The Hedgehog （Hh） signaling pathway plays important roles in both embryonic development and adult tissue homeostasis. Such biological functions are mediated by the transcription factor Cubitus interruptus （Ci）. Yet the transcriptional regulation of the effector Ci itself is poorly investigated. Through an RNAi-based genetic screen, we identified that female sterile （1） homeotic （Fsh）, a transcription co-activator, directly activates Ci transcription. Biochemistry assays demonstrated physical interactions among Fsh, Sex combs extra （Sce）, and Polycomb （Pc）. Functional assays further showed that both Pc and Sce are required for Ci expression, which is not likely mediated by the derepression of Engraited （En）, a repressor of Ci, in Pc or Sce mutant cells. Finally, we provide evidence showing that Pc/Sce facilitates the binding of Fsh at Ci locus and that the physical interaction between Fsh and Pc is essential for Fsh-mediated Ci transcription. Taken together, we not only uncover that Ci is transcriptionally regulated by Fsh-Pc-Sce complex but also provide evidence for the coordination between Fsh and PcG proteins in transcriptional regulation.
