Chromatin Assembly Factor-1

CAF-1 (chromatin assembly factor-1) is a complex, including Chaf1a (p150), Chaf1b (p60) and p50 subunits that assembles histone tetramers onto replicating DNA in vitro This complex is histone chaperone involved in creating cellular memory of somatic cell identity – cellular differentiation. CAF-1 mediates the first step in nucleosome formation by tetramerization and depositing newly synthesized histone H3/H4 onto DNA rapidly behind replication forks. Several studies have shown that the interaction between CAF-1 and PCNA, which stabilizes CAF-1 at replication forks, is important for CAF-1's role in nucleosome assembly CAF-1 (chromatin assembly factor-1) is a complex, including Chaf1a (p150), Chaf1b (p60) and p50 subunits that assembles histone tetramers onto replicating DNA in vitro This complex is histone chaperone involved in creating cellular memory of somatic cell identity – cellular differentiation. CAF-1 mediates the first step in nucleosome formation by tetramerization and depositing newly synthesized histone H3/H4 onto DNA rapidly behind replication forks. Several studies have shown that the interaction between CAF-1 and PCNA, which stabilizes CAF-1 at replication forks, is important for CAF-1's role in nucleosome assembly CAF-1 is required for the spatial organization and epigenetic marking of heterochromatin domains in pluripotent embryonic cells. Cells resembling 2-cell-stage mouse embryos (totipotent cells) can be induced in vitro through downregulation of the chromatin-assembly activity of CAF-1 in embryonic stem cells. Optimal modulation of both CAF-1 and transcription factor levels increases reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Suppression of CAF-1 also enhance the direct conversion of B cells into macrophages and fibroblasts into neurons.