title: Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition.
abstract: Epithelial-mesenchymal transition (EMT) is important for organ development, metastasis, cancer stemness, and organ fibrosis. Molecular mechanisms to coordinately regulate hypoxia-induced EMT remain elusive. Here, we show that HIF-1α-induced histone deacetylase 3 (hdac3) is essential for hypoxia-induced EMT and metastatic phenotypes. Change of specific chromatin states is associated with hypoxia-induced EMT. Under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression. HDAC3 also serves as an essential corepressor to repress epithelial gene expression. Knockdown of WDR5 abolishes mesenchymal gene activation but not epithelial gene repression during hypoxia. These results indicate that hypoxia induces different chromatin modifiers to coordinately regulate EMT through distinct mechanisms.
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors: Min-Zu
authors: MZ
authors: Wu
authors: Ya-Ping
authors: YP
authors: Tsai
authors: Muh-Hwa
authors: MH
authors: Yang
authors: Chi-Hung
authors: CH
authors: Huang
authors: Shyue-Yih
authors: SY
authors: Chang
authors: Cheng-Chi
authors: CC
authors: Chang
authors: Shu-Chun
authors: SC
authors: Teng
authors: Kou-Juey
authors: KJ
authors: Wu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014162:Transfection; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D011495:Histone-Lysine N-Methyltransferase; D000099186:Histone Deacetylase 3