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 is required for the spatial organization and epigenetic marking of heterochromatin domains in pluripotent embryonic cells.[4]

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.[5]

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..[6]

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: http://dx.doi.org/10.1016/0092-8674(89)90398-X
  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, 12183–12188
  4. ↑ Houlard M, Berlivet S, Probst AV, Quivy J-P, Héry P, Almouzni G, et al. (2006). CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells. PLoS Genet 2(11): e181. doi:10.1371/journal.pgen.0020181
  5. ↑ 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, 662–671 doi:10.1038/nsmb.3066
  6. ↑ Cheloufi S., Elling U., Hopfgartner B. et al., & Zuber J., Hochedlinger K. (2015). The histone chaperone CAF-1 safeguards somatic cell identity. Nature 528, 218–224 doi:10.1038/nature15749

Further reading

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