Open AccessT-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications
Author(s) -
Frederic Lluı́s,
Luigi Ombrato,
Elisa Pedone,
Stefano Pepe,
Bradley J. Merrill,
María Pía Cosma
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1017402108
Subject(s) - reprogramming , biology , induced pluripotent stem cell , epigenome , somatic cell , microbiology and biotechnology , heterochromatin , stem cell , genetics , cell , dna methylation , embryonic stem cell , chromatin , gene , gene expression
The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of β-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3−/− ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.