title: JMJD3 as an epigenetic regulator in development and disease.
abstract: Gene expression is epigenetically regulated through DNA methylation and covalent chromatin modifications, such as acetylation, phosphorylation, ubiquitination, sumoylation, and methylation of histones. Histone methylation state is dynamically regulated by different groups of histone methyltransferases and demethylases. The trimethylation of histone 3 (H3K4) at lysine 4 is usually associated with the activation of gene expression, whereas trimethylation of histone 3 at lysine 27 (H3K27) is associated with the repression of gene expression. The polycomb repressive complex contains the H3K27 methyltransferase Ezh2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3). The Jumonji domain containing-3 (Jmjd3, KDM6B) and ubiquitously transcribed X-chromosome tetratricopeptide repeat protein (UTX, KDM6A) have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3. The role and mechanisms of both JMJD3 and UTX have been extensively studied for their involvement in development, cell plasticity, immune system, neurodegenerative disease, and cancer. In this review, we will focus on recent progresses made on understanding JMJD3 in the regulation of gene expression in development and diseases. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Jana S
authors.initials: JS
authors.lastname: Burchfield
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Qingtian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, NY 10065, USA. Electronic address: rwang3@tmhs.org.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics* / Q000276:immunology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000276:immunology; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000276:immunology
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C523998:KDM6A protein, human; C524220:KDM6B protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine
keywords: H3K27; Histone demethylation; Jmjd3; Jumonji; Utx