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Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns
Author(s) -
Caiafa Paola,
Guastafierro Tiziana,
Zampieri Michele
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-123265
Subject(s) - dna methylation , epigenetics , chromatin , histone , epigenomics , dna methyltransferase , poly adp ribose polymerase , dnmt1 , methylation , acetylation , dna , biology , chemistry , microbiology and biotechnology , methyltransferase , polymerase , biochemistry , gene , gene expression
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 (PARylation)—participates in the establishment and maintenance of a genome methylation pattern. We hypothesize that the right nuclear balance between unmodified and PARylated poly(ADP‐ribose) polymerase 1 (PARP‐1), which depends on the dynamics of PARPs/PARG activity, is key to maintaining genomic methylation pattern. According to our data, decreased or increased levels of PARylated PARP‐1 are responsible for diffuse hypermethylation or hypomethylation of DNA, respectively. In our model, polymers present on PARP‐1 interact noncovalently with DNA methyltransferase 1 (Dnmt1), preventing its enzymatic activity. In the absence of PARylated PARP‐1, Dnmt1 is free to methylate DNA; if, in contrast, high levels of PARylated PARP‐1 persist, Dnmt1 will be stably inhibited, preventing DNA methylation.—Caiafa, P., Guastafierro, T., Zampieri, M. Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns. FASEB J. 23, 672–678 (2009)