ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement
| Autor: | Tiziana Guastafierro, Anna Reale, Oliviano Martella, Angela Catizone, Margherita Miccheli, Dawn Farrar, Fabio Ciccarone, Maria Di Girolamo, Michele Zampieri, Roberta Calabrese, Maria Giulia Bacalini, Paola Caiafa, Elena Klenova |
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| Přispěvatelé: | Guastafierro, Tiziana, Catizone, Angela, Calabrese, Roberta, Zampieri, Michele, Martella, Oliviano, Bacalini, Maria Giulia, Reale, Anna, Di Girolamo, Maria, Miccheli, Margherita, Farrar, Dawn, Klenova, Elena, Ciccarone, Fabio, Caiafa, Paola |
| Rok vydání: | 2013 |
| Předmět: |
CCCTC-Binding Factor
Glycoside Hydrolase Poly (ADP-Ribose) Polymerase-1 CCCTC-binding factor (Ctcf) chromatin structure poly(ADP-ribose) glycohydrolase (Parg) poly(ADP-ribose) polymerase 1 (Parp1) poly(ADP-ribosyl) ation (PARylation) active transport cell nucleus adenosine diphosphate ribose amino acid substitution animals CCCTC-binding factor cell line chromatin assembly and disassembly DNA methylation gene knockdown techniques glycoside hydrolases lamins mice mutagenesis site-directed mutant proteins poly (ADP-ribose) polymerase-1 Poly(ADP-ribose) polymerase Inhibitors poly(ADP-ribose) polymerases recombinant fusion proteins repressor proteins Biochemistry Poly(ADP-ribose) Polymerase Inhibitor Mice 0302 clinical medicine PARP1 Mutant Protein Cell Nucleu Poly(ADP-ribose) Polymerase 0303 health sciences PARG Poly(ADP-ribose) glycohydrolase (Parg) Active Transport Cell Nucleu Cell biology Chromatin medicine.anatomical_structure 030220 oncology & carcinogenesis Poly ADP ribose polymerase Biology Chromatin structure Cell Line 03 medical and health sciences Poly(ADP-ribose) polymerase 1 (Parp1) medicine Settore BIO/10 Molecular Biology 030304 developmental biology Adenosine Diphosphate Ribose Animal Poly(ADP-ribosyl) ation (PARylation) Cell Biology DNA Methylation Repressor Protein Chromatin Assembly and Disassembly Molecular biology Cell nucleus Amino Acid Substitution CTCF Gene Knockdown Technique Mutagenesis Site-Directed Lamin Recombinant Fusion Protein |
| Zdroj: | Biochemical Journal. 449:623-630 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20121429 |
| Popis: | Ctcf (CCCTC-binding factor) directly induces Parp [poly(ADPribose) polymerase] 1 activity and its PARylation [poly(ADPribosyl) ation] in the absence of DNA damage. Ctcf, in turn, is a substrate for this post-synthetic modification and as such it is covalently and non-covalently modified by PARs (ADP-ribose polymers). Moreover, PARylation is able to protect certain DNA regions bound by Ctcf from DNA methylation. We recently reported that de novo methylation of Ctcf target sequences due to overexpression of Parg [poly(ADP-ribose)glycohydrolase] induces loss of Ctcf binding. Considering this, we investigate to what extent PARP activity is able to affect nuclear distribution of Ctcf in the present study. Notably, Ctcf lost its diffuse nuclear localization following PAR (ADP-ribose polymer) depletion and accumulated at the periphery of the nucleus where it was linked with nuclear pore complex proteins remaining external to the perinuclear Lamin B1 ring. We demonstrated that PAR depletion-dependent perinuclear localization of Ctcf was due to its blockage from entering the nucleus. Besides Ctcf nuclear delocalization, the outcome of PAR depletion led to changes in chromatin architecture. Immunofluorescence analyses indicated DNA redistribution, a generalized genomic hypermethylation and an increase of inactive compared with active chromatin marks in Parg-overexpressing or Ctcf-silenced cells. Together these results underline the importance of the cross-talk between Parp1 and Ctcf in the maintenance of nuclear organization. © The Authors Journal compilation © 2013 Biochemical Society. |
| Databáze: | OpenAIRE |
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