ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement(1).

Tiziana Guastafierro 1 Angela Catizone 2 Roberta Calabrese 1 Michele Zampieri 1 Oliviano Martella 3 Maria Giulia Bacalini 1 Anna Reale 1 Maria Di Girolamo 3 Margherita Miccheli 1 Dawn Farrar 4 Elena Klenova 4 Fabio Ciccarone 1 Paola Caiafa 1
1 Department of Cellular Biotechnologies and Haematology
2 Department of Anatomy, Histology, Forensic Medicine and Orthopedics
3 Consorzio Mario Negri Sud
4 DBS - Department of Biological Sciences
Abstract : Ctcf (CCCTC-binding factor) directly induces Parp [poly(ADP-ribose) 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [49 references]  Display  Hide  Download
https://hal-riip.archives-ouvertes.fr/pasteur-01053368
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Wednesday, July 30, 2014 - 2:36:09 PM
Last modification on : Monday, October 8, 2018 - 5:44:07 PM
Long-term archiving on: Tuesday, April 11, 2017 - 6:47:05 PM

File

Guastafierro_et_al.pdf
Publisher files allowed on an open archive
Published as BJ Immediate Publication 2 November 2012. Provided the original publication of the article, or portion of the article, is properly cited, Authors retain the following non-exclusive rights: To post a copy of the Immediate Publication (i.e. the Accepted Manuscript*) at the Author's Institutional Repository, 6 months after publication, provided that this is linked to the article on the journal website (e.g. through the DOI).

Identifiers

Collections

RIIP | RIIP_FCB

Citation

Tiziana Guastafierro, Angela Catizone, Roberta Calabrese, Michele Zampieri, Oliviano Martella, et al.. ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement(1).. Biochemical Journal, Portland Press, 2013, 449 (3), pp.623-30. ⟨10.1042/BJ20121429⟩. ⟨pasteur-01053368⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

118

Files downloads

242

Contact

Informations

CCSD