M phase-specific interaction of DNA methyltrasferases, dnmt3a and dnmt3b, with chromosomes

Abstract

DNA cytosine methyltransferases which are DNMT1, dnmt3a, dnmt3b have been intensively studied during interphase, specially, at S-phase in that these enzymes might methylate CpG sites of chromosomes at DNA replication foci. In fact, DNMTI has been found to be targeted to replication foci and methylate Cytosine bases of CpG sequence during DNA replication. However, dnmt3a, dnmt3b have not been targeted to replication sites. Also, people suggest that these enzymes may have different roles other than methylation of CpG sites. Taken together with these facts, both dnmt3a and dnmt3b have two domains known as PWWP and PHD fingers whose functions are known as association with mitotic chromosomes. Here, we report that these two enzymes show diffuse patterning in nucleoplasm and that they are colocalized with interphase chromosomes and still continued to interact with chromosomes even at mitosis as predicted by domains present in these two proteins. Surprisingly, targetting sites of these two proteins are not the methyl CpG sites and shows no more overlapping pattern with HP1 alpha protein in adult human somatic cells different from that in mouse ES and NIH 3T3 cells, In contrary to this result, DNMT1 is not targeted to mitotic chromosomes and seems to be located at cytoplasmic compartment which is outside of chromosomes during mitosis even though this protein has CXXC zinc finger motif which binds with DNA. Also, the reasons that underlies these phenomenons are disscussed in this paper.