Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns

  title={Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns},
  author={Paola Caiafa and T. Guastafierro and Michele Zampieri},
  journal={The FASEB Journal},
  pages={672 - 678}
In the postgenome era, attention is being focused on those epigenetic modifications that modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most appropriate time to meet cellular requirements. Data reviewed show that along the chain of events that induce DNA methylation‐dependent chromatin condensation/decondensation, a postsynthetic modification other than histone acetylation, phosphorylation, and methylation—namely poly(ADP‐ribosyl)ation… 

Epigenetic Insights on PARP-1 Activity in Cancer Therapy

The potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance is discussed.

Poly(ADP-Ribosyl)ation Affects Histone Acetylation and Transcription

Results show an important link between PARylation and histone acetylation regulated transcription and a role for PARP in the inhibition of histone deacetylases.

ADP-ribose polymers localized on Ctcf–Parp1–Dnmt1 complex prevent methylation of Ctcf target sites

It is shown that Ctcf forms a complex with Dnmt1 and PARylated Parp1 at specific Ctcf target sequences and that PARylation is responsible for the maintenance of the unmethylated status of some Ctcf-bound CpGs.

Poly-ADP-Ribose (PAR) as an epigenetic flag

In the last decade, many studies have strongly indicated that alterations in epigenetic modifications may contribute to the onset and progression of a variety of human diseases such as cancer, and the enzymes responsible for these chromatin changes are becoming attractive therapeutic targets.

Poly ( ADP-ribosyl ) ation is involved in the epigenetic control of TET 1 gene transcription

ParP activity is shown to be a transcriptional regulator of TET1 gene through the control of epigenetic events and it is suggested that deregulation of these mechanisms could account for Tet1 repression in cancer.

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

ParP activity is shown to be a transcriptional regulator of TET1 gene through the control of epigenetic events and it is suggested that deregulation of these mechanisms could account for Tet1 repression in cancer.

Poly(ADP-Ribose) Polymerase 1: Cellular Pluripotency, Reprogramming, and Tumorogenesis

The biological significance of Parp1 in transcription and the epigenetic modulation of Par p1 in pluripotent status, reprogramming process and cancer will be summarized.

The PARP family: insights into functional aspects of poly (ADP‐ribose) polymerase‐1 in cell growth and survival

This review assesses current developments in PARP‐1 biology and activation signals for PARp‐1, other than conventional DNA damage activation, and focuses on its other equally important overlooked functions during growth, metabolic regulation, spermatogenesis, embryogenesis, epigenetics and differentiation.

Poly ADP-ribosylation of SET8 leads to aberrant H4K20 methylation in mammalian nuclear genome

It is shown SET8, the only known enzyme for H4K20me1 is post-translationally poly ADP-ribosylated by PARP1 on lysine residues, which renders it catalytically compromised, and degradation via ubiquitylation pathway.



CCCTC-binding Factor Activates PARP-1 Affecting DNA Methylation Machinery*S⃞

It is shown that transient ectopic overexpression of CCCTC-binding factor (CTCF) induces PAR accumulation, PARP-1, and CTCF poly(ADP-ribosyl)ation in the same mouse fibroblasts, and in vitro data show that CTCf is able to activate PARp-1 automodification even in the absence of nicked DNA.

Reduced levels of poly(ADP‐ribosyl)ation result in chromatin compaction and hypermethylation as shown by cell‐by‐cell computer‐assisted quantitative analysis

  • A. de CapoaF. Febbo P. Caiafa
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1999
The quantitative analysis allowed us to demonstrate that blocking of the poly(ADP‐ribosyl)ation results in a higher number, size, and density of antibody binding regions in treated cells when compared to the controls, as shown by cell‐by‐cell computer‐assisted quantitative analysis.

Poly(ADP-ribosyl)ation and Epigenetics: Is CTCF PARt of the Plot?

It is pointed out that the turnover of the PARlation mark at DNA-bound CTCF is indicative of a novel mode of rheostat control of expression domains possibly by regulating the stability of higher order chromatin conformations.

The PARP superfamily

This review summarizes the present knowledge of this emerging superfamily of Poly(ADP‐ribose) polymerases, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders.

Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation

It is suggested that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.

The role of poly(ADP-ribose) in the DNA damage signaling network.

A number of proteins, including histones, DNA topoisomerases, DNA methyltransferase-1 as well as DNA damage repair and checkpoint proteins (p23, p21, DNA-PK, NF-kB, XRCC1, and others) can be targeted in this manner; the interaction involves a specific poly(ADP-ribose)-binding sequence motif of 20-26 amino acids in the target domains.

Poly(ADP-ribosyl)ated chromatin domains: access granted

A general role for nuclear poly(ADP-ribosyl)ation in many aspects of genomic activity is supported, notably with the response to DNA damage, and to transcription and the maintenance of genomic stability.

Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation.

  • W. Kraus
  • Biology
    Current opinion in cell biology
  • 2008

Inhibition of poly(ADP‐ribosyl)ation introduces an anomalous methylation pattern in transfected foreign DNA

It is confirmed that poly(ADP‐ribosyl)ation is a process tightly involved in protecting genomic DNA from full methylation and the use of 3‐aminobenzamide is suggested as a possible experimental strategy to mime other conditions of DNA hypermethylation in cells.