Various in vitro and in vivo studies have highlighted the role of epigenetics on chromatin conformation and gene expression occurring upon neural development. KRAB-containing zinc finger protein ZFP57 is involved in the maintenance of parent-of-origin-dependent epigenetic state, DNA methylation and histone-tail-specific modifications of hundreds of imprinted loci in mouse. ZFP57 associates with KAP1 (general co-repressor of the KRAB-ZFPs) that acts as a recruiter of chromatin modifiers including histone H3 methyltransferase SETDB1 and heterochromatin protein-1(HP1), thus promoting H3 trimethylation at lysine9 and chromoprotein recruitment at targeted sites. DNA methyltransferases are also present in KAP1 complexes. This finding correlates with the requirement for ZFP57 to maintain DNA methylation at imprinting control regions (ICRs). This study focuses on the role of ZFP57/KAP1 in imprinting maintenance and epigenome regulation during neurogenesis and differentiation in a mouse model. We have established the genome wide occupancy of ZFP57 and associated chromatin modifiers KAP1, Hp1g and H3K9me3 and correlated with DNA methylation in murine embryonal stem cells (ESC). ZFP57, while strongly expressed in ESCs and down regulated during differentiation, was observed to be highly expressed during embryogenesis notably in the developing brain. The strong and sustained expression in the nervous system of the developing murine embryo is related to its association to ICRs, extending its potential role beyond that of maintenance of imprints during pre-implantation. We report data regarding initial studies detailing the influence and dynamics of ZFP57/KAP1 epigenetic/omic dependent signature and gene expression studies on ESCs (undifferentiated and differentiated cells toward neural fate) and developing/post-natal brain.
Genome-wide profiling of the imprinting maintenance factor ZFP57 and associated chromatin regulators in murine embryonal stem cells at imprinted and non-imprinted loci and its role in the neural development of the mouse embryo
S Filosa;G Bellenchi;A Simeone;A Riccio;C Angelini;G Grimaldi
2014
Abstract
Various in vitro and in vivo studies have highlighted the role of epigenetics on chromatin conformation and gene expression occurring upon neural development. KRAB-containing zinc finger protein ZFP57 is involved in the maintenance of parent-of-origin-dependent epigenetic state, DNA methylation and histone-tail-specific modifications of hundreds of imprinted loci in mouse. ZFP57 associates with KAP1 (general co-repressor of the KRAB-ZFPs) that acts as a recruiter of chromatin modifiers including histone H3 methyltransferase SETDB1 and heterochromatin protein-1(HP1), thus promoting H3 trimethylation at lysine9 and chromoprotein recruitment at targeted sites. DNA methyltransferases are also present in KAP1 complexes. This finding correlates with the requirement for ZFP57 to maintain DNA methylation at imprinting control regions (ICRs). This study focuses on the role of ZFP57/KAP1 in imprinting maintenance and epigenome regulation during neurogenesis and differentiation in a mouse model. We have established the genome wide occupancy of ZFP57 and associated chromatin modifiers KAP1, Hp1g and H3K9me3 and correlated with DNA methylation in murine embryonal stem cells (ESC). ZFP57, while strongly expressed in ESCs and down regulated during differentiation, was observed to be highly expressed during embryogenesis notably in the developing brain. The strong and sustained expression in the nervous system of the developing murine embryo is related to its association to ICRs, extending its potential role beyond that of maintenance of imprints during pre-implantation. We report data regarding initial studies detailing the influence and dynamics of ZFP57/KAP1 epigenetic/omic dependent signature and gene expression studies on ESCs (undifferentiated and differentiated cells toward neural fate) and developing/post-natal brain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
