Poly(ADP-ribosyl)ation is involved in the epigenetic control of  TET1  gene transcription

Fabio Ciccarone; Elisabetta Valentini; Maria Giulia Bacalini; Michele Zampieri; Roberta Calabrese; Tiziana Guastafierro; Germano Mariano; Anna Reale; Claudio Franceschi; Paola Caiafa

doi:10.18632/oncotarget.1905

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Research Papers:

Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene transcription

Fabio Ciccarone _, Elisabetta Valentini, Maria Giulia Bacalini, Michele Zampieri, Roberta Calabrese, Tiziana Guastafierro, Germano Mariano, Anna Reale, Claudio Franceschi and Paola Caiafa

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Oncotarget. 2014; 5:10356-10367. https://doi.org/10.18632/oncotarget.1905

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Abstract

Fabio Ciccarone1,2, Elisabetta Valentini1,2, Maria Giulia Bacalini3, Michele Zampieri1,2, Roberta Calabrese1,2, Tiziana Guastafierro1,2, Germano Mariano1,2, Anna Reale1,2, Claudio Franceschi3 and Paola Caiafa1,2

1 Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Rome, Italy

2 Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy

3 Department of Experimental Pathology, Alma Mater Studiorum, University of Bologna, Bologna, Italy

Correspondence:

Fabio Ciccarone, email:

Paola Caiafa, email:

Keywords: poly(ADP-ribosyl)ation, TET1, DNA methylation, 5-hydroxymethylcytosine

Received: February 07, 2014 Accepted: April 16, 2014 Published: April 17, 2014

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 expressionmaintaining 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.

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Research Papers:

Poly(ADP-ribosyl)ation is involved in the epigenetic control of TET1 gene transcription

Abstract