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Epigenetic Lineage Barriers ensure normal Trophoblast Differentiation in Early Development
Author(s) -
Hemberger Myriam C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.403.2
Subject(s) - trophoblast , lineage (genetic) , epigenetics , biology , dna methylation , embryonic stem cell , placenta , genetics , genomic imprinting , methylation , microbiology and biotechnology , cellular differentiation , gene , evolutionary biology , fetus , gene expression , pregnancy
Cells that give rise to the trophoblast lineage are set aside in the earliest differentiation event after fertilization to mediate implantation, placenta formation and fetal nutrition. We are interested in genetic and epigenetic factors that contribute to normal trophoblast differentiation and formation of a functional placenta. Correlating with the global asymmetry in DNA methylation levels between cells of the embryonic and trophoblast lineage, we have found that DNA methylation is critical to ensure the stability of early cell lineage determination. In a genome‐wide screen for promoter DNA methylation differences, we have identified a gatekeeper gene, Elf5 , that is unmethylated and expressed in the trophoblast lineage, but methylated and stably repressed in the embryonic lineage. We show that this gatekeeper acts downstream of initial lineage determination to either reinforce commitment to the trophoblast lineage, or to abort this pathway in the embryonic lineage. This finding is the first example of a major epigenetic restriction of cell lineage fate and provides a molecular mechanism for the concept of canalization of developmental pathways during embryogenesis. This work was supported by the MRC, BBSRC and the Centre for Trophoblast Research.