The epigenetic modifier Fam208a is required to maintain epiblast cell fitness

0486353 - ÚMG 2018 RIV GB eng J - Journal Article
Bhargava, Shohag - Cox, B. - Polydorou, Ch. - Grešáková, Veronika - Kořínek, Vladimír - Strnad, Hynek - Sedláček, Radislav - Epp, Trevor Allan - Chawengsaksophak, Kallayanee
The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.
Scientific Reports. Roč. 7, léto (2017), č. článku 9322. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA ČR GA15-23165S; GA MŠMT LO1419; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) LM2011032; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LQ1604
Institutional support: RVO:68378050
Keywords : bone morphogenetic protein-4 * position-effect variegation * gastrulating mouse embryo * anterior-posterior axis * mesoderm differentiation * expression pattern * mice lacking * postimplantation development * definitive endoderm * primitive streak
OECD category: Biochemistry and molecular biology
Impact factor: 4.122, year: 2017

Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.
Permanent Link: http://hdl.handle.net/11104/0281183