title: Oocyte-specific linker histone H1foo is an epigenomic modulator that decondenses chromatin and impairs pluripotency.
abstract: Mammalian oocytes contain the histone H1foo, a distinct member with low sequence similarity to other members in the H1 histone family. Oocyte-specific H1foo exists until the second embryonic cell stage. H1foo is essential for oocyte maturation in mice; however, the molecular function of this H1 subtype is unclear. To explore the function of H1foo, we generated embryonic stem (ES) cells ectopically expressing H1foo fused to an EGFP (H1foo-ES). Interestingly, ectopic expression of H1foo prevented normal differentiation into embryoid bodies (EBs). The EB preparations from H1foo-ES cells maintained the expression of pluripotent marker genes, including Nanog, Myc and Klf9, and prevented the shift of the DNA methylation profile. Because the short hairpin RNA-mediated knockdown of H1foo-EGFP recovered the differentiation ability, H1foo was involved in preventing differentiation. Furthermore, ChIP analysis revealed that H1foo-EGFP bound selectively to a set of hypomethylated genomic loci in H1foo-ES, clearly indicating that these loci were targets of H1foo. Finally, nuclease sensitivity assay suggested that H1foo made these target loci decondensed. We concluded that H1foo has an impact on the genome-wide, locus-specific epigenetic status.
authors.affiliation: Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Jun
authors.initials: J
authors.lastname: Ohgane
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yagi
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D058732:Embryoid Bodies / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism; D034741:RNA, Small Interfering; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers; C423383:H1f8 protein, mouse; D006657:Histones; D034741:RNA, Small Interfering