Transcription Factor IIA τ Is Associated with Undifferentiated Cells and Its Gene Expression Is Repressed in Primary Neurons at the Chromatin Level In Vivo

The levels of General Transcription Factor (TF) IIA were examined during mammalian brain development and in rat embryo fibroblasts and transformed cell lines. The large TFIIA subunit paraloguesαβ and τ are largely produced in unsynchronized cell lines, yet only TFIIA αβ is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA τ, αβ, and γ subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec cells required replating to induce a neuronal phenotype and loss of detectable TFIIA τ and γ proteins. High levels of TFIIA τ, αβ, and γ and Sp factors were identified in extracts from human fetal and rat embryonic day-18 brains, but not in human and rat adult brain extracts. A high histone H3 Lys9/Lys4 methylation ratio was observed in the TFIIA τ promoter of primary hippocampal neurons from day-18 rat embryos, suggesting that repressive epigenetic marks of chromatin prevent TFIIA τ from being transcribed in neurons. We conclude that TFIIA τ is associated with undifferentiated cells during development, yet is down-regulated at the chromatin level upon cellular differentiation.