5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP-1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins.

5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme / Ciccarone, Fabio; Valentini, Elisabetta; Zampieri, Michele; Caiafa, Paola. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 6:27(2015), pp. 24333-24347. [10.18632/oncotarget.4476]

5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme

CICCARONE, FABIO;VALENTINI, ELISABETTA;ZAMPIERI, Michele;CAIAFA, Paola
2015

Abstract

5-hydroxymethylcytosine is a new epigenetic modification deriving from the oxidation of 5-methylcytosine by the TET hydroxylase enzymes. DNA hydroxymethylation drives DNA demethylation events and is involved in the control of gene expression. Deregulation of TET enzymes causes developmental defects and is associated with pathological conditions such as cancer. Little information thus far is available on the regulation of TET activity by post-translational modifications. Here we show that TET1 protein is able to interact with PARP-1/ARTD1 enzyme and is target of both noncovalent and covalent PARylation. In particular, we have demonstrated that the noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. Collectively, our results highlight a complex interplay between PARylation and TET1 which may be helpful in coordinating the multiple biological roles played by 5-hydroxymethylcytosine and TET proteins.
2015
5hmC; PARylation; TET1
01 Pubblicazione su rivista::01a Articolo in rivista
5mC-hydroxylase activity is influenced by the PARylation of TET1 enzyme / Ciccarone, Fabio; Valentini, Elisabetta; Zampieri, Michele; Caiafa, Paola. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 6:27(2015), pp. 24333-24347. [10.18632/oncotarget.4476]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/837745
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