H1f8, also known as H1foo, is an oocyte-specific linker histone. Linker histones are involved in higher-order chromatin structure, and H1foo plays a crucial role in regulating chromatin structure during oogenesis and early embryogenesis [4,5]. It may control gene expression presumably through perturbing chromatin structure [4,5].

In one-cell-stage mouse embryos, H1foo knockdown causes the chromatin structure in the pronucleus to be tighter and increases deposition of histone H3 variant H3.1/3.2 in the peripheral region of the pronucleus. Overexpressing H1foo in two-cell-stage embryos lessens the decrease in chromatin looseness, suggesting its role in changing chromatin structure via nuclear deposition of H3 variants between these two stages [1]. In induced pluripotent stem cells (iPSCs), induction of H1foo with Oct4, Sox2, and Klf4 significantly enhances the efficiency of iPSC generation, promotes in vitro differentiation with low heterogeneity, and enhances the generation of germline-competent chimeric mice from iPSCs, indicating its contribution to generating higher-quality iPSCs [2]. Ectopic expression of H1foo in embryonic stem (ES) cells prevents normal differentiation into embryoid bodies, maintains the expression of pluripotent marker genes, and prevents the shift of the DNA methylation profile. ChIP analysis shows H1foo-EGFP binds selectively to a set of hypomethylated genomic loci, and nuclease sensitivity assay suggests it makes these target loci decondensed, meaning H1foo impacts the genome-wide, locus-specific epigenetic status [3].

In conclusion, H1foo is essential for regulating chromatin structure in early embryonic development and has a significant impact on processes like iPSC generation and maintaining the epigenetic status. The study of H1foo knockout or conditional knockout mouse models has revealed its functions in these biological processes, contributing to our understanding of early development and pluripotency-related mechanisms.