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Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of Trophoblast Stem Cells

ABSTRACT: Derivation and maintenance of TS cells depends on the presence of Fgf signalling. Numerous gene knock-out experiments identified the mitogen activated kinase Mek/Erk branch of the Fgf signalling pathway as predominantly active in both TS cells and extraembryonic ectoderm. Therefore, we tested changes in expression of the key TS cell transcription factors (TFs) upon Mek/Erk inhibition using the Mek inhibitor PD0325901 (“PD03”). To obtain an unbiased genome-wide coverage of the immediate-early response genes of Mek inhibition in TS cells, we performed RNA-seq analysis after 3h and 24h of PD03 treatment. Notably, of the known TS cell TFs, this analysis confirmed Esrrb as the earliest, most rapidly silenced gene upon PD03 treatment. In order to gain first insights into which genes may be primary targets of Esrrb, we treated TS cells with the synthetic nonsteroidal estrogen diethylstilbestrol (DES), an estrogen-related receptor (Err) antagonist and also performed RNA-seq upon short (24h) and prolonged (4d) DES treatment. Finally, to obtain a comprehensive global overview of the binding sites of Esrrb in TS cells, and of its interaction with Lsd1 and Nr0b1 (Dax1), we performed chromatin immunoprecipitation (ChIP)-seq experiments on these factors.

INSTRUMENT(S): Illumina HiSeq 1000

ORGANISM(S): Mus musculus

SUBMITTER: Angela Goncalves

PROVIDER: E-MTAB-3565 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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