title: Snail2/Slug cooperates with Polycomb repressive complex 2 (PRC2) to regulate neural crest development.
abstract: Neural crest cells arise from the border of the neural plate and epidermal ectoderm, migrate extensively and differentiate into diverse cell types during vertebrate embryogenesis. Although much has been learnt about growth factor signals and gene regulatory networks that regulate neural crest development, limited information is available on how epigenetic mechanisms control this process. In this study, we show that Polycomb repressive complex 2 (PRC2) cooperates with the transcription factor Snail2/Slug to modulate neural crest development in Xenopus. The PRC2 core components Eed, Ezh2 and Suz12 are expressed in the neural crest cells and are required for neural crest marker expression. Knockdown of Ezh2, the catalytic subunit of PRC2 for histone H3K27 methylation, results in defects in neural crest specification, migration and craniofacial cartilage formation. EZH2 interacts directly with Snail2, and Snail2 fails to expand the neural crest domains in the absence of Ezh2. Chromatin immunoprecipitation analysis shows that Snail2 regulates EZH2 occupancy and histone H3K27 trimethylation levels at the promoter region of the Snail2 target E-cadherin. Our results indicate that Snail2 cooperates with EZH2 and PRC2 to control expression of the genes important for neural crest specification and migration during neural crest development.
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Tien
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
authors.forename: Hengbin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
authors.forename: Magda
authors.initials: M
authors.lastname: Gerigk
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Nozell
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Avenue S., Birmingham, AL 35294, USA cchang@uab.edu.
authors.forename: Chenbei
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C561115:SNAI2 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; D063151:Polycomb Repressive Complex 2
keywords: EZH2; Neural crest; Polycomb repressive complex 2 (PRC2); Snail2/Slug; Xenopus