Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression

Abstract

Transcription initiation is a key regulatory step in the control of gene expression. Formation of a preinitiation complex at the right time and at the right promoter is a prerequisite to executing the correct programs of mRNA synthesis. This involves the interplay of many transcription factors and a combinatorial array of cis-regulatory DNA elements. Recent findings suggest that metazoan organisms have evolved specialized transcription initiation complexes and promoter-selectivity modules that direct coordinated regulation of functionally related gene networks. Here, we summarize corroborating evidence for a highly diversified core transcription machinery directing cell type-specific and gene-selective transcription. In multicellular organisms elaborate mechanisms have evolved to control the spatial and temporal patterns of transcription during growth, differentiation, and development. Transcriptional activation, one of the fundamental means of regulating gene expression in eukaryotes, is governed by an interconnected ensemble of multisubunit transcription factor complexes (Fig. 1; Lemon and Tjian 2000; Narlikar et al. 2002; Orphanides and Reinberg 2002). To assure the proper assembly of the transcription machinery, the components of the core transcriptional apparatus and the chromatin DNA template are subject to regulation. For instance, a variety of covalent histone and DNA modifications can influence whether a chromatin template is programmed to be transcriptionally active or silent (Strahl and Allis 2000; Berger 2002; Geiman and Robertson 2002). Also, numerous chromatin remodeling/nucleosome mobilizing activities catalyze the ATP-dependent deposition, removal, or sliding of nucleosomes to generate DNA templates that are accessible to the transcription machinery (Becker and Horz 2002). An enormous family of DNA sequence-specific transcriptional activators working in concert with various coregulatory factors drive the formation of active transcription initiation complexes (Lemon and Tjian 2000; Malik and Roeder 2000; Naar et al. 2001). It now seems clear that this highly regulated and coordinated assembly of active transcription complexes requires the interplay of a large number of transcription factors, multiple core promoter elements, and chromatin remodeling and modifying factors to properly position the preinitiation complex (PIC) at the start site of RNA synthesis (Burley and Roeder 1996; Roeder 1996; Lemon and Tjian 2000; Fig. 1). Until recently, the general transcription machinery that makes up the PIC was thought to be largely invariant when compared among different cell types within an organism. Although a large number of tissue-specific transcription factors have been described that control expression of cell type-specific genes, most of these have been enhancer-binding transcription factors. However, contrary to expectations, several studies have identified cell type-specific components of the core transcription machinery. Subsequently, an increasing number of cell type-specific and gene-selective homologs of basal transcription factors have been identified in metazoan organisms, including additional members of the TATA boxbinding protein (TBP) family such as TBP-related factors (TRFs) as well as numerous tissue-specific homologs of TBP-associated factors (TAFs). It now seems apparent that multicellular organisms have evolved cell type-specific components of the general transcriptional apparatus as a mechanism to accommodate more complex programs of tissue-specific and gene-selective transcription. Intriguingly, many of these functionally specialized core promoter factors are subunits of TFIID. This central component of the PIC harbors several transcription factors directly involved in recognizing and binding core promoter elements such as the TATA box, Initiator (Inr), and downstream promoter element (DPE). These findings suggest that metazoans have evolved functionally specialized transcription initiation complexes and promoter-selective modules, which might serve as eukaryotic factors (Gross et al. 1998; Losick 1998). In this review, we will summarize some recent advances in our understanding of how these specialized transcription initiation complexes might mediate proCorresponding author. EMAIL jmlim@uclink4.berkeley.edu; FAX (510) 643-9547. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1099903.