Transcription Factor IIA tau 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 paralogues alphabeta and tau are largely produced in unsynchronized cell lines, yet only TFIIA alphabeta is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA tau, alphabeta, and gamma 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 tau and gamma proteins. High levels of TFIIA tau, alphabeta, and gamma 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 tau promoter of primary hippocampal neurons from day-18 rat embryos, suggesting that repressive epigenetic marks of chromatin prevent TFIIA tau from being transcribed in neurons. We conclude that TFIIA tau is associated with undifferentiated cells during development, yet is down-regulated at the chromatin level upon cellular differentiation.
Howe
Mariko L
ML
Department of Pharmacology and Experimental Therpeutics, Boston University School of Medicine, MA 02118, USA.
Mehmud
Zareen F
ZF
Saha
Shamol
S
Buratovich
Michael
M
Stutius
Erica A
EA
Schmidt
Heath D
HD
Lenon
Angela L
AL
Reddicks
Candice
C
Ivanov
Gleb S
GS
Przyborski
Stefan A
SA
Ozer
Josef S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D019073:HT29 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051703:Sp Transcription Factors / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D035561:Transcription Factor TFIIA / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D002087:Butyrates; D002843:Chromatin; D006657:Histones; D021122:Protein Subunits; D051703:Sp Transcription Factors; D035561:Transcription Factor TFIIA; D014212:Tretinoin