Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo.
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.
Maki
Nobuyasu
N
Department of Biology, University of Dayton, Dayton, OH 45469-2320, USA. makinobu@notes.udayton.edu
Suetsugu-Maki
Rinako
R
Sano
Shozo
S
Nakamura
Kenta
K
Nishimura
Osamu
O
Tarui
Hiroshi
H
Del Rio-Tsonis
Katia
K
Ohsumi
Keita
K
Agata
Kiyokazu
K
Tsonis
Panagiotis A
PA
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
D006657:Histones; D038222:gamma-Crystallins
Biol Reprod. 2005 Jan;72(1):135-42
15371275
Nat Rev Genet. 2002 Sep;3(9):662-73
12209141
Mol Biol Cell. 2005 Aug;16(8):3887-95
15944219
Development. 2001 Mar;128(5):655-64
11171391
Mol Cell Biol. 1997 Mar;17(3):1189-200
9032246
Mol Cell Biol. 1995 Feb;15(2):653-60
7823934
Eur J Biochem. 2002 May;269(9):2284-7
11985609
Dev Dyn. 2007 Apr;236(4):941-50
17133523
Biotechniques. 2008 Dec;45(6):613-4, 616, 618 passim
19238792
Int J Dev Biol. 2009;53(2-3):215-24
19247968
Genes Dev. 2002 Dec 1;16(23):2991-3003
12464630
Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
16261189
Dev Biol. 2004 Feb 1;266(1):76-86
14729479
Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5697-702
15821029
Dev Biol. 2004 Feb 1;266(1):62-75
14729478
Mech Dev. 2002 Sep;117(1-2):253-7
12204266
Mech Dev. 2002 Sep;117(1-2):249-52
12204265
Gene. 1994 Jun 10;143(2):233-8
8206379
Dev Growth Differ. 1977;19(4):309-317
37281713
Mol Reprod Dev. 2006 Jun;73(6):692-9
16470586
Genes Cells. 2002 Jul;7(7):693-706
12081646
Proc Natl Acad Sci U S A. 1973 May;70(5):1495-9
4576021
Science. 2004 Jun 11;304(5677):1675-8
15192231
Can J Biochem. 1964 Dec;42:1743-52
14241608