title: Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene transcription.
abstract: TET enzymes are the epigenetic factors involved in the formation of the sixth DNA base 5-hydroxymethylcytosine, whose deregulation has been associated with tumorigenesis. In particular, TET1 acts as tumor suppressor preventing cell proliferation and tumor metastasis and it has frequently been found down-regulated in cancer. Thus, considering the importance of a tight control of TET1 expression, the epigenetic mechanisms involved in the transcriptional regulation of TET1 gene are here investigated. The involvement of poly(ADP-ribosyl)ation in the control of DNA and histone methylation on TET1 gene was examined. PARP activity is able to positively regulate TET1 expression maintaining a permissive chromatin state characterized by DNA hypomethylation of TET1 CpG island as well as high levels of H3K4 trimethylation. These epigenetic modifications were affected by PAR depletion causing TET1 down-regulation and in turn reduced recruitment of TET1 protein on HOXA9 target gene. In conclusion, this work shows that PARP activity is a transcriptional regulator of TET1 gene through the control of epigenetic events and it suggests that deregulation of these mechanisms could account for TET1 repression in cancer.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciccarone
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Valentini
authors.affiliation: Department of Experimental Pathology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zampieri
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Calabrese
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Guastafierro
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Germano
authors.initials: G
authors.lastname: Mariano
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Reale
authors.affiliation: Department of Experimental Pathology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy. Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caiafa
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D061986:MCF-7 Cells; D006899:Mixed Function Oxygenases; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; C097899:homeobox protein HOXA9; D000244:Adenosine Diphosphate; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D011065:Poly(ADP-ribose) Polymerases