Chaf1b, also known as chromatin assembly factor 1 subunit B or the p60 subunit of the chromatin-assembly factor-1 (CAF-1) complex, is crucial for nucleosome assembly following DNA synthesis, maintaining genomic stability [4]. It has multiple functional domains like the 7× WD repeat domain, B-like domain, and a PEST domain, but how these contribute to its functions is not fully clear. It is involved in various biological processes such as DNA synthesis and repair [3,6].

In mouse pre-implantation embryos, Chaf1b knockdown led to a low blastocyst hatching rate, outgrowth failure in vitro, and embryonic lethality in vivo. It increased apoptosis and down-regulated key cell fate specification regulators. Mechanistically, it mediated the replacement of H3.3 with H3.1/3.2, affecting histone marks and chromatin accessibility [2]. In myeloproliferative neoplasms (MPN), Chaf1b is overexpressed. Targeted silencing enhanced IFNα-stimulated gene transcription and promoted IFNα-dependent antineoplastic responses in primary MPN progenitor cells [1]. In nasopharyngeal carcinoma, high Chaf1b levels correlated with radioresistance. Silencing Chaf1b enhanced radiosensitivity by promoting apoptosis and inhibiting DNA damage repair in a DNA-PK pathway-dependent manner [3]. In leukemia, overexpression of Chaf1b displaced myeloid transcription factors from chromatin, while its deletion promoted leukemia cell differentiation and suppressed leukemogenesis in a murine model [5,7].

In summary, Chaf1b plays significant roles in embryo development, hematopoiesis, and cancer-related processes. Mouse models, especially gene knockout or conditional knockout models, have been instrumental in revealing its functions in these biological processes and disease conditions, highlighting its potential as a therapeutic target in diseases like MPN, nasopharyngeal carcinoma, and leukemia.