CAF-1 (chromatin assembly factor-1) is a complex consisting of three subunits: Chaf1a (p150), Chaf1b (p60) and p50. This complex transfers the tetramer (four) of H3 / H4 histones to replicating DNA [1] [2] [3] . CAF-1 is involved in the creation of cellular epigenetic memory necessary to maintain the individual traits ( differentiation ) of somatic cells .
CAF-1 is required for the spatial organization and epigenetic labeling of heterochromatin domains in pluripotent embryonic stem cells [4] .
By suppressing the activity of CAF-1 necessary for chromatin assembly, embryonic stem cells can be transferred to the totipotency state characteristic of early embryos of the 2-cell stage [5] .
The selection of the optimal level of CAF-1 and transcription factors can increase the efficiency of reprogramming by several orders of magnitude and reduce the duration of reprogramming in iPSCs to only 4 days. Obviously, the inhibition of CAF-1 activity leads to the formation of a more accessible chromatin structure in enhancer sites during the early stages of reprogramming. These changes are accompanied by a decrease in the number of somatic heterochromatin domains, an increase in Sox2 binding to pluripotency regions, and activation of the corresponding genes. Suppression of CAF-1 also increases the efficiency of direct transdifferentiation of B cells into macrophages and fibroblasts into neurons [6] .
Notes
- ↑ 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
- ↑ 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: https://dx.doi.org/10.1016/0092-8674(89)90398-X
- ↑ 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
- ↑ Houlard M, Berlivet S, Probst AV, Quivy JP, 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
- ↑ Ishiuchi, T., Enriquez-Gasca, R., Mizutani, E., Bošković, A., Ziegler-Birling, C., Rodriguez-Terrones, D., ... & Torres-Padilla, ME (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
- ↑ 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
Literature
- Memory loss enables the production of stem cells . Scienceday
- Yu, Z., Liu, J., Deng, WM, & Jiao, R. (2015). Histone chaperone CAF-1: essential roles in multi-cellular organism development . Cellular and Molecular Life Sciences, 72 (2), 327-337. DOI : 10.1007 / s00018-014-1748-3
- Kaufman, PD (2015). Want reprogramming? Cut back on the chromatin assembly !. Nature structural & molecular biology, 22 (9), 648-650. DOI : 10.1038 / nsmb.3081
- Polo, SE, & Almouzni, G. (2015). Chromatin dynamics after DNA damage: The legacy of the access – repair – restore model. DNA repair. 36, 114–121 DOI : 10.1016 / j.dnarep.2015.09.09.014