title: Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells.
abstract: Expression of Oct3/4, Sox2, Klf4, and c-Myc (OSKM) can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Somatic cell nuclear transfer (SCNT) can also be used for reprogramming, suggesting that factors present in oocytes could potentially augment OSKM-mediated induction of pluripotency. Here, we report that two histone variants, TH2A and TH2B, which are highly expressed in oocytes and contribute to activation of the paternal genome after fertilization, enhance OSKM-dependent generation of iPSCs and can induce reprogramming with Klf4 and Oct3/4 alone. TH2A and TH2B are enriched on the X chromosome during the reprogramming process, and their expression in somatic cells increases the DNase I sensitivity of chromatin. In addition, Xist deficiency, which was reported to enhance SCNT reprogramming efficiency, stimulates iPSC generation using TH2A/TH2B in conjunction with OSKM, but not OSKM alone. Thus, TH2A/TH2B may enhance reprogramming by introducing processes that normally operate in zygotes and during SCNT.
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Functional Genomics, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: sinagawa@rtc.riken.jp.
authors: Toshie
authors: T
authors: Shinagawa
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors: Tsuyoshi
authors: T
authors: Takagi
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors: Daisuke
authors: D
authors: Tsukamoto
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Functional Genomics, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Chinatsu
authors: C
authors: Tomaru
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Functional Genomics, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Linh My
authors: LM
authors: Huynh
authors: RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors: Padavattan
authors: P
authors: Sivaraman
authors: RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors: Thirumananseri
authors: T
authors: Kumarevel
authors: RIKEN BioResource Center, Tsukuba 305-0074, Japan.
authors: Kimiko
authors: K
authors: Inoue
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; CREST, JST, K's Gobancho, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Ryuichiro
authors: R
authors: Nakato
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; CREST, JST, K's Gobancho, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Yuki
authors: Y
authors: Katou
authors: Medical Institute of Bioregulation, Kyushu University, 812-8582 Fukuoka, Japan.
authors: Takashi
authors: T
authors: Sado
authors: Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors: Satoru
authors: S
authors: Takahashi
authors: RIKEN BioResource Center, Tsukuba 305-0074, Japan.
authors: Atsuo
authors: A
authors: Ogura
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan; CREST, JST, K's Gobancho, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Laboratory of Molecular Genetics, CREST Research Project of JST (Japan Science and Technology Agency), RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan; Department of Functional Genomics, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. Electronic address: sishii@rtc.riken.jp.
authors: Shunsuke
authors: S
authors: Ishii
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016678:Genome / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D020033:Protein Isoforms; D012333:RNA, Messenger