Editing Epigenetics (section)

====Homologous recombinational repair alters epigenetic markers====
At least four articles report the recruitment of [[DNA methyltransferase|DNA methyltransferase 1 (DNMT1)]] to sites of DNA double-strand breaks.<ref name="pmid15956212">{{cite journal |vauthors=Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H |title=Recruitment of DNA methyltransferase I to DNA repair sites |journal=Proc Natl Acad Sci U S A |volume=102 |issue=25 |pages=8905–9 |date=June 2005 |pmid=15956212 |pmc=1157029 |doi=10.1073/pnas.0501034102 |bibcode=2005PNAS..102.8905M |url=|doi-access=free }}</ref><ref name=Cuozzo>{{cite journal |vauthors=Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV |title=DNA damage, homology-directed repair, and DNA methylation |journal=PLOS Genet |volume=3 |issue=7 |pages=e110 |date=July 2007 |pmid=17616978 |pmc=1913100 |doi=10.1371/journal.pgen.0030110 |url= |doi-access=free }}</ref><ref name="pmid18704159">{{cite journal |vauthors=O'Hagan HM, Mohammad HP, Baylin SB |title=Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island |journal=PLOS Genet |volume=4 |issue=8 |pages=e1000155 |date=August 2008 |pmid=18704159 |pmc=2491723 |doi=10.1371/journal.pgen.1000155 |url= |doi-access=free }}</ref><ref name="pmid20940144">{{cite journal |vauthors=Ha K, Lee GE, Palii SS, Brown KD, Takeda Y, Liu K, Bhalla KN, Robertson KD |title=Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery |journal=Hum Mol Genet |volume=20 |issue=1 |pages=126–40 |date=January 2011 |pmid=20940144 |pmc=3000680 |doi=10.1093/hmg/ddq451 |url=}}</ref> During [[homologous recombination|homologous recombinational repair (HR)]] of the double-strand break, the involvement of DNMT1 causes the two repaired strands of DNA to have different levels of methylated cytosines. One strand becomes frequently methylated at about 21 [[CpG site]]s downstream of the repaired double-strand break. The other DNA strand loses methylation at about six CpG sites that were previously methylated downstream of the double-strand break, as well as losing methylation at about five CpG sites that were previously methylated upstream of the double-strand break. When the chromosome is replicated, this gives rise to one daughter chromosome that is heavily methylated downstream of the previous break site and one that is unmethylated in the region both upstream and downstream of the previous break site. With respect to the gene that was broken by the double-strand break, half of the progeny cells express that gene at a high level and in the other half of the progeny cells expression of that gene is repressed. When clones of these cells were maintained for three years, the new methylation patterns were maintained over that time period.<ref name="pmid27629060">{{cite journal |vauthors=Russo G, Landi R, Pezone A, Morano A, Zuchegna C, Romano A, Muller MT, Gottesman ME, Porcellini A, Avvedimento EV |title=DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism |journal=Sci Rep |volume=6 |issue= |pages=33222 |date=September 2016 |pmid=27629060 |pmc=5024116 |doi=10.1038/srep33222 |bibcode=2016NatSR...633222R |url=}}</ref>

In mice with a CRISPR-mediated homology-directed recombination insertion in their genome there were a large number of increased methylations of CpG sites within the double-strand break-associated insertion.<ref name="pmid33267773">{{cite journal |vauthors=Farris MH, Texter PA, Mora AA, Wiles MV, Mac Garrigle EF, Klaus SA, Rosfjord K |title=Detection of CRISPR-mediated genome modifications through altered methylation patterns of CpG islands |journal=BMC Genomics |volume=21 |issue=1 |pages=856 |date=December 2020 |pmid=33267773 |pmc=7709351 |doi=10.1186/s12864-020-07233-2 |url= |doi-access=free }}</ref>