title: Retinoic acid dependent histone 3 demethylation of the clustered HOX genes during neural differentiation of human embryonic stem cells.
abstract: Gene activation of HOX clusters is an early event in embryonic development. These genes are highly expressed and active in the vertebrate nervous system. Based on the presence of retinoic acid response elements (RAREs) in the regulatory region of many of the HOX genes, it is deduced that retinoic acid (RA) can influence epigenetic regulation and consequently the expression pattern of HOX during RA-induced differentiation of embryonic model systems. In this investigation, the expression level as well as the epigenetic regulation of several HOX genes of the 4 A-D clusters was analyzed in human embryonic stem cells, and also through their neural induction, in the presence and absence of RA. Expression analysis data significantly showed increased mRNA levels of all examined HOX genes in the presence of RA. Epigenetic analysis of the HOX gene regulatory regions also showed a significant decrease in methylation of histone H3K27 parallel to an absolute preferential incorporation of the demethylase UTX rather than JMJD3 in RA-induced neural differentiated cells. This finding clearly showed the functional role of UTX in epigenetic alteration of HOX clusters during RA-induced neural differentiation; the activity could not be detectable for the demethylase JMJD3 during this developmental process.
authors.affiliation: Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, P.O. Box 19395-4644, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shahhoseini
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Taghizadeh
authors.forename: Maryam
authors.initials: M
authors.lastname: Hatami
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014212:Tretinoin; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C523998:KDM6A protein, human; C524220:KDM6B protein, human