Transcriptional Regulatory Mechanisms in Animal Cells

Abstract

Transcriptional regulation by gene‐ and cell‐specific DNA‐binding factors underlies key events in development and in cell growth, differentiation and transformation. Whereas animal cells contain thousands of these factors, their stimulatory or inhibitory effects on the general transcription machinery (RNA polymerases and cognate initiation factors) on specific target genes depend upon complex arrays of cofactors (coactivators and corepressors) that add additional layers of regulation. These cofactors include both chromatin remodeling/histone modifying factors (including various histone acetyltransferases and methyltransferases) and factors (such as the 30‐subunit Mediator complex and the TAF subunits of TFIID) that facilitate more direct communication between promoter‐bound regulatory factors and the general transcription machinery. Most recently, the laboratory has employed biochemically defined cell‐free systems reconstituted with recombinant chromatin templates and purified factors (containing over 90 distinct polypeptides) to identify and to analyze both independent and cooperative functions of diverse types of cofactors, as well as underlying mechanisms.The function of Mediator, TFIID/TAFs, and selected cell‐specific coactivators and histone modifying factors will be discussed in relation to gene activation by specific transcription factors.