title: Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo.
abstract: The ability to reprogram in vivo a somatic cell after differentiation is quite limited. One of the most impressive examples of such a process is transdifferentiation of pigmented epithelial cells (PECs) to lens cells during lens regeneration in newts. However, very little is known of the molecular events that allow newt cells to transdifferentiate. Histone B4 is an oocyte-type linker histone that replaces the somatic-type linker histone H1 during reprogramming mediated by somatic cell nuclear transfer (SCNT). We found that B4 is expressed and required during transdifferentiation of PECs. Knocking down of B4 decreased proliferation and increased apoptosis, which resulted in considerable smaller lens. Furthermore, B4 knockdown altered gene expression of key genes of lens differentiation and nearly abolished expression of gamma-crystallin. These data are the first to show expression of oocyte-type linker histone in somatic cells and its requirement in newt lens transdifferentiation and suggest that transdifferentiation in newts might share common strategies with reprogramming after SCNT.
authors.affiliation: Department of Biology, University of Dayton, Dayton, OH 45469-2320, USA. makinobu@notes.udayton.edu
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Maki
authors.forename: Rinako
authors.initials: R
authors.lastname: Suetsugu-Maki
authors.forename: Shozo
authors.initials: S
authors.lastname: Sano
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tarui
authors.forename: Katia
authors.initials: K
authors.lastname: Del Rio-Tsonis
authors.forename: Keita
authors.initials: K
authors.lastname: Ohsumi
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Agata
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Tsonis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D053652:Nuclear Transfer Techniques; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012455:Salamandridae / Q000235:genetics / Q000378:metabolism*; D038222:gamma-Crystallins / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D038222:gamma-Crystallins
references.citation: Biol Reprod. 2005 Jan;72(1):135-42
references.pmid: 15371275
references.citation: Nat Rev Genet. 2002 Sep;3(9):662-73
references.pmid: 12209141
references.citation: Mol Biol Cell. 2005 Aug;16(8):3887-95
references.pmid: 15944219
references.citation: Development. 2001 Mar;128(5):655-64
references.pmid: 11171391
references.citation: Mol Cell Biol. 1997 Mar;17(3):1189-200
references.pmid: 9032246
references.citation: Mol Cell Biol. 1995 Feb;15(2):653-60
references.pmid: 7823934
references.citation: Eur J Biochem. 2002 May;269(9):2284-7
references.pmid: 11985609
references.citation: Dev Dyn. 2007 Apr;236(4):941-50
references.pmid: 17133523
references.citation: Biotechniques. 2008 Dec;45(6):613-4, 616, 618 passim
references.pmid: 19238792
references.citation: Int J Dev Biol. 2009;53(2-3):215-24
references.pmid: 19247968
references.citation: Genes Dev. 2002 Dec 1;16(23):2991-3003
references.pmid: 12464630
references.citation: Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
references.pmid: 16261189
references.citation: Dev Biol. 2004 Feb 1;266(1):76-86
references.pmid: 14729479
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5697-702
references.pmid: 15821029
references.citation: Dev Biol. 2004 Feb 1;266(1):62-75
references.pmid: 14729478
references.citation: Mech Dev. 2002 Sep;117(1-2):253-7
references.pmid: 12204266
references.citation: Mech Dev. 2002 Sep;117(1-2):249-52
references.pmid: 12204265
references.citation: Gene. 1994 Jun 10;143(2):233-8
references.pmid: 8206379
references.citation: Dev Growth Differ. 1977;19(4):309-317
references.pmid: 37281713
references.citation: Mol Reprod Dev. 2006 Jun;73(6):692-9
references.pmid: 16470586
references.citation: Genes Cells. 2002 Jul;7(7):693-706
references.pmid: 12081646
references.citation: Proc Natl Acad Sci U S A. 1973 May;70(5):1495-9
references.pmid: 4576021
references.citation: Science. 2004 Jun 11;304(5677):1675-8
references.pmid: 15192231
references.citation: Can J Biochem. 1964 Dec;42:1743-52
references.pmid: 14241608