title: Identification of a functional estrogen-responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines.
abstract: The retinoblastoma protein-interacting zinc-finger (RIZ) gene, also known as PRDM2, encodes two protein products, RIZ1 and RIZ2, differing for the presence of a 202 aa domain, called PR domain, at the N-terminus of the RIZ1 molecule. While the histone H3 K9 methyltransferase activity of RIZ1 is associated with the negative control of cell proliferation, no information is currently available on either expression regulation of the RIZ2 form or on its biological activity. RIZ proteins act as ER co-activators and promote optimal estrogen response in female reproductive tissues. In estrogen-responsive cells, 17-β estradiol modulates RIZ gene expression producing a shift in the balanced expression of the two forms. Here, we demonstrate that an estrogen-responsive element (ERE) within the RIZ promoter 2 is regulated in a ligand-specific manner by ERα, through both the AF1 and AF2 domains. The pattern of ERα binding, histone H4 acetylation, and histone H3 cyclical methylation of lysine 9 was comparable to other estrogen-regulated promoters. Association of topoisomerase IIβ with the RIZ promoter 2 confirmed the transcriptional activation induced by estrogen. We hypothesize that RIZ2, acting as a negative regulator of RIZ1 function, mediates the proliferative effect of estrogen through regulation of survival and differentiation gene expression.
authors.affiliation: Dipartimento di Patologia generale, Seconda Università degli studi di Napoli, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Abbondanza
authors.forename: Caterina
authors.initials: C
authors.lastname: De Rosa
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Arcangelo
authors.forename: Marianna
authors.initials: M
authors.lastname: Pacifico
authors.forename: Clorinda
authors.initials: C
authors.lastname: Spizuoco
authors.forename: Giulio
authors.initials: G
authors.lastname: Piluso
authors.forename: Erika
authors.initials: E
authors.lastname: Di Zazzo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gazzerro
authors.forename: Nicola
authors.initials: N
authors.lastname: Medici
authors.forename: Bruno
authors.initials: B
authors.lastname: Moncharmont
authors.forename: Giovanni Alfredo
authors.initials: GA
authors.lastname: Puca
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004958:Estradiol; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human