Alternative titles; symbols
HGNC Approved Gene Symbol: CHAF1B
Cytogenetic location: 21q22.12-q22.13 Genomic coordinates (GRCh38): 21:36,385,392-36,419,015 (from NCBI)
Chromatin assembly factor I (CAF1) is a 3-subunit nuclear complex consisting of p50, p60, and p150 (CHAF1A; 601246) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995).
Kaufman et al. (1995) obtained a cDNA for p60 using partial amino acid sequence data from purified protein. The predicted 559-amino acid protein belongs to the WD (tryptophan-aspartate), or transducin, family (see 139330). These proteins are generally characterized by 4 to 8 copies of a repeat of approximately 40 residues that often ends with a WD sequence (p60 has 7 copies of the motif). The p60 subunit also has a PEST (proline-glutamic acid-serine-threonine) box at its C terminus that is associated with proteins of short half-lives.
Kaufman et al. (1995) found that the p150 and p60 subunits interact with each other during nucleosome assembly and deletion of the p60 binding domain from p150 abolishes chromatin assembly. Kaufman et al. (1995) also showed that p150 and p60 form complexes with newly synthesized histone H3 (see 601058) and acetylated histone H4 (see 602822), which may form an intermediate prior to assembly on replicating DNA.
To elucidate regulatory pathways that safeguard the somatic state, Cheloufi et al. (2015), performed 2 comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the CAF1 complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF1 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 (184429) to pluripotency-specific targets, and activation of associated genes. Notably, suppression of CAF1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. The findings of Cheloufi et al. (2015) revealed the histone chaperone CAF1 to be a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provided a potential strategy to modulate cellular plasticity in a regenerative setting.
Blouin et al. (1996) mapped the CHAF1B gene to 21q22.2 by correspondence of its sequence to that of an exon trapped from the Down syndrome critical region. Katsanis and Fisher (1996) confirmed the location of the gene, which they called CAF1P60, using PCR to amplify the 3-prime untranslated region of the gene in a monochromosomal hybrid panel and in a high-resolution radiation hybrid panel. In addition, they carried out PCR analysis of a collection of chromosome 21 YACs. They demonstrated that the CHAF1B gene maps to 21q22.2 between D21S333 and D21S334.
Blouin, J.-L., Duriaux-Sail, G., Chen, H., Gos, A., Morris, M. A., Rossier, C., Antonarakis, S. E. Mapping of the gene for the p60 subunit of the human chromatin assembly factor (CAF1A) to the Down syndrome region of chromosome 21. Genomics 33: 309-312, 1996. [PubMed: 8660983] [Full Text: https://doi.org/10.1006/geno.1996.0199]
Cheloufi, S., Elling, U., Hopfgartner, B., Jung, Y. L., Murn, J., Ninova, M., Hubmann, M., Badeaux, A. I., Ang, C. E., Tenen, D., Wesche, D. J., Abazova, N., and 24 others. The histone chaperone CAF-1 safeguards somatic cell identity. Nature 528: 218-224, 2015. [PubMed: 26659182] [Full Text: https://doi.org/10.1038/nature15749]
Katsanis, N., Fisher, E. M. C. The gene encoding the p60 subunit of chromatin assembly factor I (CAF1P60) maps to human chromosome 21q22.2, a region associated with some of the major features of Down syndrome. Hum. Genet. 98: 497-499, 1996. [PubMed: 8792829] [Full Text: https://doi.org/10.1007/s004390050246]
Kaufman, P. D., Kobayashi, R., Kessler, N., Stillman, B. The p150 and p60 subunits of chromatin assembly factor I: a molecular link between newly synthesized histones and DNA replication. Cell 81: 1105-1114, 1995. [PubMed: 7600578] [Full Text: https://doi.org/10.1016/s0092-8674(05)80015-7]