Oncotarget

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

PDF  |  HTML  |  Supplementary Files  |  How to cite

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

Metrics: PDF 2825 views  |   HTML 3694 views  |   ?  


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 Franceschiand 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1905