title: The Proto-oncogene Transcription Factor Ets1 Regulates Neural Crest Development through Histone Deacetylase 1 to Mediate Output of Bone Morphogenetic Protein Signaling.
abstract: The neural crest (NC) is a transient, migratory cell population that differentiates into a large variety of tissues including craniofacial cartilage, melanocytes, and peripheral nervous system. NC is initially induced at the border of neural plate and non-neural ectoderm by balanced regulation of multiple signaling pathways among which an intermediate bone morphogenetic protein (BMP) signaling is essential for NC formation. ets1, a proto-oncogene playing important roles in tumor invasion, has also been implicated in delamination of NC cells. In this study, we investigated Ets1 function in NC formation using Xenopus. Overexpression of ets1 repressed NC formation through down-regulation of BMP signaling. Moreover, ets1 repressed the BMP-responsive gene id3 that is essential for NC formation. Conversely, overexpression of id3 can partially rescue the phenotype of NC inhibition induced by ectopic ets1. Mechanistically, we found that Ets1 binds to id3 promoter as well as histone deacetylase 1, suggesting that Ets1 recruits histone deacetylase 1 to the promoter of id3, thereby inducing histone deacetylation of the id3 promoter. Thus, our studies indicate that Ets1 regulates NC formation through attenuating BMP signaling epigenetically.
authors.affiliation: From the School of Biomedical Sciences and.
authors.forename: Chengdong
authors.initials: C
authors.lastname: Wang
authors.affiliation: From the School of Biomedical Sciences and.
authors.forename: Richard Kin Ting
authors.initials: RK
authors.lastname: Kam
authors.affiliation: Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Shi
authors.affiliation: From the School of Biomedical Sciences and Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Advanced Biomedical Computing Center, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Xiongfong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Model Animal Research Center of Nanjing University and Ministry of Education Key Laboratory of Model Animals for Disease Study, 12 Xuefu Road, Pukou High-Tech Zone, Nanjing 210061, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Translational Cancer Research and Stem Cell Center, Department of Laboratory Medicine, Lund University, Medicon Village, 22381 Lund, Sweden, and.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 845 Lingshan Road, Shanghai 200135, China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Du
authors.affiliation: From the School of Biomedical Sciences and Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 845 Lingshan Road, Shanghai 200135, China.
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the School of Biomedical Sciences and Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
authors.forename: Wood Yee
authors.initials: WY
authors.lastname: Chan
authors.affiliation: From the School of Biomedical Sciences and Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China.
authors.forename: Sun On
authors.initials: SO
authors.lastname: Chan
authors.affiliation: Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: From the School of Biomedical Sciences and Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China, zhaohui@cuhk.edu.hk.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; C501325:Id3 protein, Xenopus; D051796:Inhibitor of Differentiation Proteins; C529423:Lrig3 protein, Xenopus; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D029867:Xenopus Proteins; D056284:Histone Deacetylase 1
keywords: BMP; ETS transcription factor family; Id3; Xenopus; bone morphogenetic protein (BMP); embryo; histone deacetylase (HDAC); neural crest; signal transduction