Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells.

Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical ...
to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.
Mesh Terms:
Animals, Cell Differentiation, Cell Line, Embryonic Stem Cells, Epigenesis, Genetic, Fibroblast Growth Factors, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Histone Demethylases, MAP Kinase Signaling System, Mice, Protein Interaction Mapping, RNA Polymerase II, Receptors, Estrogen, Trophoblasts
Nat Commun
Date: Jul. 24, 2015
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