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Sci Rep. 2016 Sep 15;6:33222. doi: 10.1038/srep33222.

DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism.

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Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
Epigenetics Division, TopoGEN, Inc., 27960 CR319, Buena Vista, Colorado, 81211, USA.
Institute of Cancer Research, Columbia University Medical Center, New York, New York, 10032, USA.


We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5' and 3' ends of the repaired gene. During a two-week period after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes further modifies methylation of the repaired DNA. Subsequently, the repaired genes display stable but diverse methylation profiles. These profiles govern the levels of expression in each clone. Our data argue that DNA methylation and chromatin remodelling induced by HR may be a source of permanent variation of gene expression in somatic cells.

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