Epigenomic analysis of the imprinting factor ZFP57, KRAB-ZFPs corepressor KAP1 and associated chromatin modifiers by ChIP seq in mouse embrional stem cells

Several lines of evidence have provided clues for the pivotal role played by the KRAB- containing zinc finger protein ZFP57 in the establishment and maintenance of the asymmetric epigenetic state, both DNA methylation and histone tails specific modifications, of the several tens of imprinted loci in mouse. ZFP57 associates with KAP1, the general corepressor of the abundant KRAB-ZFPs family, a scaffold for the recruitment of chromatin modifiers that include the histone H3 methyltransferase SETDB1 and heterochromatin protein-1 (HP1) isoforms, thus promoting H3 trimethylation at lysine 9 and chromoproteins assembly at targeted sites. Further, DNA methyltransferases are also present in KAP1 complexes, a finding that correlates with the requirement for ZFP57 to mantain DNA methylation at targeted sites. We have established in murine ES cells the epigenomic profile of the endogenous Zfp57 factor along with those of the associated KAP1, SETDB1, HP1g and the complex-dependent H3K9 trimethylation. We will report on the DNA binding motifs inference, features of bound genomic targets along with the gene association analysis that support potential pivotal roles of the locus-specific targeting ZFP57 factor in shaping the epigenetic state of multiple genes in addition to imprinted loci, through histone modification, Hp1-mediated heterochromatinization and DNA methylation.