Estrogen-related receptor beta differentially regulates target genes through diverse interactions with DNA, TFIIH, and coactivators

Estrogen-related receptor (ERR) beta is critical for maintenance of mouse embryonic stem cell (ESC) self-renewal under 2-inhibitor (“2i”) conditions. On the other hand, we biochemically revealed ERR activated transcription through the interaction with DNA, TFIIA, and C-terminal AF2 domain binding coactivators. To evaluate the biological significance of this finding, we analyzed the transcriptome of DNA-, TFIIH-, and coactivator-binding deficient mutant ERR beta-expressing ERR beta-knockout ESCs which showed compromised self-renewal activity. The results demonstrated that each interaction was required for regulating the specific biological/functional gene set among ERR beta-target genes. Established ERR beta-knockout ESC clones doxycycline-inducibly expressing wild-type, DNA-, TFIIH-, and coactivator-binding deficient mutant ERR beta, and wild-type ERR gamma-expressing ERR beta-knockout were cultured in N2B27-PD/CH medium and doxycycline for 3 days, total RNA was used for RNA-seq analysis.