ZFP57/KAP1 Genomic Association and Targeted Epigenetic Regulation at Imprinted and Not Imprinted Loci

ZFP57, a KRAB- containing zinc finger protein, plays a pivotal role in the maintenance of the parent of origin-dependent epigenetic state, DNA methylation and histone tails specific modifications, of the several imprinted loci in mouse, through the association with known imprinting control regions (ICRs). ZFP57 associates with KAP1, the general corepressor of the abundant KRAB-ZFPs family, a recruiter of chromatin modifiers, namely the histone H3 methyltransferase SETDB1 and heterochromatin protein-1 (HP1) isoforms, thus promoting H3 trimethylation at lysine 9 and chromoproteins assembly at targeted sites. Furthermore, DNA methyltransferases are also present in KAP1 complexes, a finding that correlates with the requirement for ZFP57 to maintain DNA methylation at ICRs and its dependence on DNA methylation of sequence-specific exameric targets for binding. Our aim is to study the role of ZFP57/KAP1 in imprinting maintenance, epigenome regulation and potential role in neurogenesis and differentiation in a mouse model. Genome-wide chromatin analyses show that ZFP57 associates to several hundred loci in murine embryonal stem cells (ESCs) indicating a wider epigenomic/etic role than just ICR imprinting maintenance. Apart from the expression in the zygote and early embryonic pre-implantation stages, ZFP57 is also espressed later during embryo development at specific regions, notably in the nervous system. We report data regarding initial studies on the influence, dynamics and fate of ZFP57/KAP1 epigenetic/omic dependent signature, with a focus on the potential connection to specific factors involved in writing and reading DNA methylation marks, by the use of ESCs (undifferentiated and differentiated cells toward neural fate) and of developing/post-natal brain.