CAF-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[1][2][3] 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[4] 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[5]

CAF-1 is required for the spatial organization and epigenetic marking of heterochromatin domains in pluripotent embryonic cells.[6]

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.[7]

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.[8]

References

  1. ↑ Kaufman PD, Kobayashi R, Kessler N, Stillman B (1995). "The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication". Cell. 81 (7): 1105–14. doi:10.1016/S0092-8674(05)80015-7. PMID 7600578.
  2. ↑ Smith S, Stillman B (1989). "Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro". Cell. 58 (1): 15–25. doi:10.1016/0092-8674(89)90398-X. PMID 2546672.
  3. ↑ Hoek, M.; Stillman, B. (2003). "Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo". Proc. Natl. Acad. Sci. USA. 100 (21): 12183–12188. doi:10.1073/pnas.1635158100. PMID 14519857.
  4. ↑ Liu, W. H.; Roemer, S. C.; Zhou, Y; Shen, Z. J.; Dennehey, B. K.; Balsbaugh, J. L.; Liddle, J. C.; Nemkov, T; Ahn, N. G.; Hansen, K. C.; Tyler, J. K.; Churchill, M. E. (2016). "The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones". ELife. 5: e18023. doi:10.7554/eLife.18023. PMC 5045291Freely accessible. PMID 27690308.
  5. ↑ Zhang, K; Gao, Y; Li, J; Burgess, R; Han, J; Liang, H; Zhang, Z; Liu, Y (2016). "A DNA binding winged helix domain in CAF-1 functions with PCNA to stabilize CAF-1 at replication forks". Nucleic Acids Research. 44 (11): 5083–5094. doi:10.1093/nar/gkw106. PMC 4914081Freely accessible. PMID 26908650.
  6. ↑ Houlard, Martin; Berlivet, Soizik; Probst, Aline V.; Quivy, Jean-Pierre; Héry, Patrick; Almouzni, Geneviève; Gérard, Matthieu (2006). "CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells". PLoS Genet. 2 (11): e181. doi:10.1371/journal.pgen.0020181.
  7. ↑ Ishiuchi, T.; Enriquez-Gasca, R.; Mizutani, E.; Bošković, A.; Ziegler-Birling, C.; Rodriguez-Terrones, D.; Torres-Padilla, M. E. (2015). "Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly". Nature Structural & Molecular Biology. 22 (9): 662–671. doi:10.1038/nsmb.3066.
  8. ↑ Cheloufi S, Elling U, Hopfgartner B, et al. (2015). "The histone chaperone CAF-1 safeguards somatic cell identity". Nature. 528 (7581): 218–224. doi:10.1038/nature15749. PMC 4866648Freely accessible. PMID 26659182.

Further reading

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